levoleucovorin and Stomach-Neoplasms

In the last two decades, the incidence of gastroesophageal junction (GEJ) adenocarcinomas (AC) has increased, in part due to the increasing prevalence of obesity and untreated gastroesophageal reflux disease (GERD). Esophageal and GEJ cancers have become one of the leading causes of cancer deaths worldwide due to its aggressive nature. While the mainstay of treatment for locally advanced gastroesophageal cancers (GECs) remains surgery, several studies have now shown that multimodality approach yields better outcomes. GEJ cancers have historically been included both in esophageal cancer as well as gastric cancer trials. Therefore, both approaches, neoadjuvant chemoradiation (CRT) or perioperative chemotherapy are considered standard treatment options. thereon the same token, there yet remains a debate for the 'gold standard' treatment of locally advanced GEJ cancers. The landmark trials, fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) and ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), have shown similar improvements in overall survival (OS) and disease-free survival (DFS) for patients with resectable locoregional GEJ cancers. In this review, the authors attempt to highlight the historical evolution of current standard treatments and provide a sneak peek into the future of treatment of GEJ cancers. Several factors must be borne in mind when making the optimal choice for a patient. Some of these include surgical candidacy, tolerance to chemotherapy, eligibility for radiation (RT) as well as institutional preferences.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Stomach Neoplasms

BACKGROUND Gastric cancer metastasis to the appendix is a rare condition that might present with symptoms of acute appendicitis or remain asymptomatic and be diagnosed incidentally. This report summaries 6 previously reported cases in addition to the presented case. CASE REPORT We report a 54-years-old female patient who presented with gastric cancer metastasis to the appendix that was found incidentally in the second surgery when she underwent bowel resection due to bowel entrapment in internal hernia, a complication of her primary gastric cancer surgical intervention. Six case-reports on gastric cancer metastasis to the appendix were reviewed. The metastasis was symptomatic in 4 cases, and solitary in 3 cases. The diagnosis was delayed in 4 cases as there was no evidence of metastasis at the diagnosis of the primary tumor; appendectomy was performed in all cases. The prognosis of the cases varied considerably. CONCLUSIONS We question the real incidence of appendiceal metastasis in gastric cancer, and the benefit-risk ratio of appendectomy in every gastrectomy. Guidelines on management of similar cases is also needed.

Topics: Adenocarcinoma; Anastomosis, Roux-en-Y; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colectomy; Delayed Diagnosis; Female; Fluorouracil; Gastrectomy; Humans; Incidental Findings; Leucovorin; Middle Aged; Missed Diagnosis; Organoplatinum Compounds; Postoperative Complications; Stomach Neoplasms

FLOT-4 study recently reports that in patients with gastric cancer, perioperative chemotherapy with 5-fluorouracile, leucovorin, oxaliplatin and docetaxel (FLOT regimen) increases survival over standard ECF/ECX regimen (epirubicine, cisplatine and 5-fluorouracile [or capecitabine]). Does this study, make FLOT a new standard of perioperative chemotherapy for localized gastric cancer? Seven hundred and sixteen patients were included into that randomized study. Thirty seven per cent and 46% of the patients received the full planned treatment in the ECF/ECX group and in the FLOT group, respectively. The primary aim of FLOT-4 was met as FLOT significantly reduced the relative risk of death vs. ECF/ECX (HR: 0.77; 95% CI: 0.63-0.94; P=0.012). Median survival is increased by 15 months with FLOT (50 months vs. 35 months). FLOT also provided better complete resection rates, better complete pathological response rates, and better disease-free survival than ECF/ECX. FLOT is more likely associated with the following adverse events: diarrheas, leuco-neutropenia (including 51% of severe ones), infections (including 18% of severe ones), and peripheral neuropathy. On the contrary, ECF/ECX provided more likely severe nausea and vomiting, severe anemia, and thromboembolic events. Overall, the number of patients with related serious adverse events (including those that occurred during hospital stay for surgery) was similar in the two groups, as was the number of toxic deaths and postoperative deaths. FLOT should be regarded as the recommended perioperative chemotherapy for patients with gastric cancer or adenocarcinoma of the gastro-esophageal junction. However, some doubts remain as regards of its use in the daily practice for unselected patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Disease-Free Survival; Docetaxel; Epirubicin; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Perioperative Care; Randomized Controlled Trials as Topic; Stomach Neoplasms

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemoradiotherapy; Dose Fractionation, Radiation; Endoscopy, Digestive System; Endosonography; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Humans; Incidence; Leucovorin; Magnetic Resonance Imaging; Organoplatinum Compounds; Pregnancy; Pregnancy Complications, Neoplastic; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cancer Pain; Chemoradiotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Endoscopy, Gastrointestinal; Fluorouracil; Gastrectomy; Gastrointestinal Hemorrhage; Humans; Ileostomy; Jejunal Neoplasms; Leucovorin; Male; Microsatellite Instability; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Positron Emission Tomography Computed Tomography; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

The study aims to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in patients with advanced gastric cancer.. Five databases were searched up to June 2014, without language restrictions. The outcomes included overall response rate (ORR), clinical benefit rate (CBR), and toxicity.. Twenty-six eligible trials were selected from 178 studies that initially were identified. All trials were published in Chinese journals between 2005 and 2014 and included 1585 patients (787 in XELOX group and 798 in FOLFOXs group). The pooled results failed to show statistical significance of XELOX regimen on ORR (OR 1.18, 95% CIs 1.00-1.41, P = 0.057) and CBR (OR 1.10, 95% CIs 0.95-1.28, P = 0.191) as compared with FOLFOXs regimen. None of the 26 clinical trials reported progression-free survival, and only one reported overall survival rate. The meta-analysis demonstrated that XELOX regimen was associated with a significant lower risk with nausea, stomatitis, diarrhea and alopecia, and a significant higher risk of hand-foot syndrome.. The evidence is limited to suggest that XELOX may share similar efficacy as FOLFOXs and reduce toxicities of chemotherapy in advanced gastric cancer therapy. However, owing to limited data and potential bias of the included studies, further rigorously controlled trials are required.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Odds Ratio; Organoplatinum Compounds; Oxaloacetates; Randomized Controlled Trials as Topic; Stomach Neoplasms

There are presented results of recently published large multicenter randomized trials on the effectiveness of different adjuvant therapy regimens after gastrectomy D2 in patients with gastric cancer. It is shown that adjuvant chemotherapy as monotherapy by drug S-1 and polychemotherapy by XELOX improves long-term outcomes of patients with stages 2-3. At the same time the intensification of therapy--additional administration of paclitaxel, the combination FOLFIRI scheme with docetaxel and cisplatin--have not led to a significant increase in survival rate. In regard of the advisability of combination of adjuvant chemotherapy and radiotherapy. The data obtained do not allow to make a define conclusion up to date. Promising areas of research is the use of targeted drugs in adjuvant regimen as well as the search for biomarkers to identify patients at high risk of recurrence and to predict the effectiveness of adjuvant therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Docetaxel; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Multicenter Studies as Topic; Oxaloacetates; Oxonic Acid; Paclitaxel; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Analysis; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Few studies have directly compared clinical efficacy and safety among Chinese herb injections (CHIs) for gastric cancer (GC). The present study aimed to compare CHIs combined with FOLFOX regimens for GC to show which provides the best CHIs results.. 9 electronic databases and 6 gray literature databases were comprehensive searched in April 20, 2013. According to inclusion and exclusion criteria, two reviewers independently selected and assessed the included trials. The risk of bias tool described in the Cochrane Handbook version 5.1.0 and CONSORT statement were used to assess the quality of the trials. All calculations and graphs were performed and produced using ADDIS 1.16.5 software.. A total of 541 records were searched and 38 RCTs met the inclusion criteria (2,761 participants), involving 10 CHIs. The results of network meta-analysis showed that compared with FOLFOX alone, combinations with Kanglaite, Astragalus polysaccharides, Cinobufacini, or Yadanziyouru injections could furthest strengthen ORR, improve the quality of life, reduce nausea and vomiting, and reduce the incidence of leukopenia (III-IV).. Kanglaite injection, Astragalus polysaccharides injection, Yadanziyouru injection were superior to other CHIs in clinical efficacy and safety for GC. The conclusions now need to be confirmed by large sample size direct head-to-head studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drugs, Chinese Herbal; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Organoplatinum Compounds; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Stomach Neoplasms

A 48-year-old man with colorectal cancer and right inguinal lymph node metastasis had previously undergone radiotherapy and chemotherapy (uracil/tegafur/leucovorin) after a colostomy in another hospital before being referred to us. Esophagogastroduodenoscopy (EGD) revealed the presence of a gastric metastatic lesion. After three courses of treatment with a modified regimen of leucovorin plus 5-fluorouracil plus oxaliplatin-6 (mFOLFOX6), EGD revealed that the gastric lesion had disappeared; computed tomography revealed that the size of the primary tumor and inguinal lymph node metastasis were markedly reduced. Subsequently, he underwent rectal resection of the primary tumor and continued treatment with mFOLFOX6 in combination with bevacizumab. We reviewed 29 similar cases from the literature, and determined that surgical resection of the tumor and appropriate chemotherapy can lead to long-term survival for patients with gastric metastases from colorectal cancer. Furthermore, positive CK20 and CDX2 expression and negative CK7 expression were useful adjuncts in the immunohistochemical diagnosis of gastric metastases from colorectal adenocarcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

To improve outcome of resectable gastric cancer, several treatment strategies have been evaluated. These include adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. The US Intergroup 0116 trial reported the benefit of postoperative chemoradiotherapy using 5-FU/leucovorin in a U.S. population. In this study, only 10 % of patients received D2 resection. For Korean patients after D2 resection, the ARTIST trial failed to show any benefit from adding radiotherapy to adjuvant chemotherapy in terms of 3-year disease-free survival. The MAGIC trial compared perioperative chemotherapy with surgery alone and reported a prolonged 5-year overall survival in the perioperative chemotherapy arm. In resectable gastric cancer, the benefit of adjuvant chemotherapy compared with surgery alone has been clearly demonstrated. After D2 dissection, S-1 adjuvant chemotherapy improved the overall survival (ACTS-GC trial) and capecitabine/oxaliplatin combination chemotherapy improved 3-year disease-free survival (CLASSIC trial). To date, for resectable gastric cancer, the use of chemotherapy in addition to surgery is beneficial for the reduction of recurrence and to improve overall survival. The optimal sequence of chemotherapy and surgery, as well as optimal chemotherapeutic agents, should be further studied. In D2-resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit.].

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Perioperative Care; Randomized Controlled Trials as Topic; Stomach Neoplasms

Bladder involvement by a secondary tumor is fairly rare and an uncommon source of bladder metastasis is the stomach.. The authors report a case of a 38-year-old man with a bladder metastasis from a gastric signet-ring-cell (SRC) adenocarcinoma who presented with ematuria. The clinical history and the presence of SRCs in the voided urinary cytology and histologically in the suburothelial connective, with an overlying intact urothelium suggested a diagnosis of bladder metastasis from gastric carcinoma.. Bladder involvement by a secondary tumor is very rare, and a SRC carcinoma metastatic to the bladder, albeit extremely rare, should be considered in the differential diagnosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cytodiagnosis; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Stomach Neoplasms; Urinary Bladder Neoplasms; Urine

Takotsubo syndrome (TTS)/cardiomyopathy is a syndrome that mimics acute myocardial infarction in the absence of coronary artery disease and is characterized by acute onset of chest pain, electrocardiographic abnormalities, and reversible left ventricular dysfunction. It is usually induced by emotional and physical stress. Fluorouracil is one of the most frequently used chemotherapy agents and a relatively common adverse reaction of fluorouracil is cardiotoxicity. Herein we describe a patient without a history of cardiovascular disorder who developed severe heart failure during infusion of fluorouracil for metastatic gastric cancer. Remarkably, the patient did not develop TTS during prior chemotherapy regimen, which also included fluorouracil. The patient's findings were consistent with the proposed TTS diagnostic criteria and coronary angiography was normal, without obstructive coronary artery disease. With supportive care, the patient's cardiac functions returned to normal. TTS is not a well known syndrome to clinicians and this condition appears to occur more frequently than previously thought. In addition to the presented case, a review of the clinical features and outcome of 10 reported cases of fluorouracil-induced TTS is presented.

Topics: Amiodarone; Anti-Arrhythmia Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Combined Modality Therapy; Coronary Angiography; Diagnostic Errors; Docetaxel; Electric Countershock; Fatal Outcome; Fluorouracil; Gastrectomy; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Myocardial Infarction; Peritoneal Neoplasms; Peritonitis; Stomach Neoplasms; Takotsubo Cardiomyopathy; Taxoids; Ventricular Fibrillation

Rapidly developing pulmonary fibrosis associated with the use of the anti-cancer drug oxaliplatin has been reported mainly by Asiatic literature as isolate case reports. This rare but potentially fatal side effect has neither identified risk factors nor established treatment guideline. We report here a new clinical case concerning a patient with advanced gastric cancer treated with the oxaliplatin-based FOLFOX regimen along with a review of the literature as well as a discussion of emerging experimental treatment mainly based on imatinib.

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzamides; Fluorouracil; Humans; Imatinib Mesylate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Piperazines; Protein Kinase Inhibitors; Pulmonary Fibrosis; Pyrimidines; Stomach Neoplasms

The patient was a 79-year-old woman. We became introduction consultation than a nearby doctor in alpha-fetoprotein(AFP)high level. Abdominal ultrasonography showed 30mm great tumor in liver lateral segment area and gastric fiber showed type2 tumor which is AFP producing gastric cancer. On admission AFP level is high(403ng/ml). Multiple liver metastases were noted it by abdominal angiography. We started FLAP(5-fluorouracil, leucovorin, etoposide, cisplatin)combination chemotherapy by a diagnosis of AFP producing gastric cancer StageIV. It is reduction of a liver tumor after one course, and the stomach lesion almost disappeared after three courses end points.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Stomach Neoplasms

Since irinotecan, S-1, docetaxel, and paclitaxel were approved, therapeutic options for chemotherapy in the treatment of gastric cancer have increased. It is suggested that the efficient use of the primary drugs prolongs life in the treatment of progressive colorectal cancer. Also, physicians have discussed ways to take full advantage of the drugs in the treatment of gastric cancer. In first-line treatment in other countries, combination therapy usually includes the administration of two drugs, while in Japan, where therapies based on S-1 have been developed, the most appropriate strategy must be determined after reporting the results of phase III trials in 2007. In the clinic, treatment must be selected on the basis of solid evidence in consideration of the organ dysfunction associated with progressive gastric cancer. The timing of any changes in the treatment should be considered because the cancer easily metastasizes to the peritoneum. Throughout the world, various regimens have been developed that replace cisplatin with oxaliplatin or mainly use oral fluoropyrimidine. Molecular target drugs, now being evaluated in phase II trials, will also be used in the treatment of gastric cancer in the near future. Novel therapies will be developed in Asia and Japan where the incidence of gastric cancer is high.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials, Phase III as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Methotrexate; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

Despite a decline in the incidence of upper gastrointestinal adenocarcinomas in North America and western Europe during the past century, treatment remains a challenging problem for oncologists. The poor outcome associated with surgical resection with curative intent has generated intensive investigation of combined modality treatment approaches including systemic chemotherapy to prevent recurrences and improve overall mortality. This article reviews data on neoadjuvant and perioperative treatment modalities for upper gastrointestinal adenocarcinomas.. Postoperative chemoradiation is favored in the USA for good performance status patients with resected, high-risk gastric or gastroesophageal junction carcinoma (more stage IA). More recently, the UK Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) and Fédération Nationale des Centres de Lutte Contre le Cancer-Fédération Francophone de Cancérologie Digestive trials results, showing survival benefit with perioperative chemotherapy in operable gastric and lower esophageal cancers, have had an impact on the treatment practice in Europe.. Novel strategies, involving induction with chemotherapy followed by preoperative chemoradiation, addition of targeted therapies to perioperative chemotherapy or use of new cytotoxic regimens are under evaluation to improve current standards and try to tailor therapeutic strategies.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Postoperative Care; Stomach Neoplasms; Time Factors

Colorectal cancers have been the first cancers to benefit from an efficient anti-angiogenic treatment, represented by bevacizumab, which has been approved for first-line metastatic treatment in combination with reference chemotherapies and which is under study in the adjuvant setting. Other gastro-intestinal malignancies appear less responsive to anti-angiogenic therapy, but inhibitors of the VEGF receptors (sorafenib, sunitinib, axitinib) are in development with encouraging results. The safety profile of anti-angiogenic agents is quite different from that of classical chemotherapy and may require a modification of treatment strategies.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoma, Hepatocellular; Colorectal Neoplasms; Esophageal Neoplasms; Fluorouracil; Gastrointestinal Neoplasms; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Neovascularization, Pathologic; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Stomach Neoplasms

Formerly the treatment of gastrointestinal cancers was exclusively surgical. Though the results were improved by increased radicality, the real progress was achieved by the introduction of multimodal therapy, particularly by the neoadjuvant concept. The basic prerequisite for neoadjuvant treatment is precise staging and risk assessment. According to staging patients can be divided into three categories: (1) Early cancers, confined to the mucosal and submucosal layers, are approached with primary surgery. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are treated by neoadjuvant therapy. Due to neoadjuvant treatment the tumor can be downsized (or downstaged) in some patients. These are the responders benefiting from the therapy, because of the increased RO-resection rate, decreased recurrence rate and improved survival. The non-responders, by contrast have poor prognosis. Neoadjuvant treatment considerably improved the chance for cure for patients with gastrointestinal cancers, thus this method became an evidence based treatment for locally advanced gastrointestinal cancers.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Esophageal Neoplasms; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Outcome in the management of clinically resectable gastric carcinoma has been disappointing, at least in Western populations, despite increasingly radical surgery and extensive experience with adjunctive perioperative treatment with innumerable single and combined modality regimens. The United States Intergroup Study, a prospective, randomized, controlled trial of adjuvant chemoradiation, demonstrated significant improvement in disease-free and overall survival. Consequently, this regimen of postoperative fluoruracil plus leucovorin and locoregional radiation has been incorporated into current clinical practice. In hopes of further improving cure rates, many other regimens are under investigation, including the efficacy of neoadjuvant therapy alone, combined neoadjuvant and adjuvant therapy, and adjuvant therapy alone. In these clinical trials, therapeutic agents are prescribed alone or in multimodal regimens and include systemic chemotherapy, intraperitoneal (IP) chemotherapy with or without hyperthermia, intraoperative radiotherapy (IORT), and postoperative external beam irradiation. Several molecular markers have been identified, which seem to predict that a given tumor may be effective or resistant to a drug, raising the possibility of customized chemotherapy regimens. Preclinical studies suggest potential efficacy of angiogenesis inhibitors, monoclonal antibodies, and antisense agents.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Fluorouracil; Gastrectomy; Humans; Irinotecan; Leucovorin; Preoperative Care; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Stomach Neoplasms

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%-80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease-free and overall survival resulting from post-operative chemoradiation have defined a new standard of care. An update of the results of INT-0116 analysis performed in 2004 with 7 years median follow-up, not only confirms the benefits from post-operative chemoradiation but also shows that chemoradiation does not produce significant long-term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might down-stage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre-operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Postoperative Period; Radiotherapy Dosage; Stomach Neoplasms; Survival Rate

The currently reported 5-year survival rates for patients with resected stage II, IIIA, IIIB, and IV gastric cancer are 34%, 20%, 8%, and 7%, respectively. A subtotal or total gastrectomy with a D1 en bloc dissection of lymphatic tissue is the standard surgical treatment. Several meta-analyses of post-operative adjuvant trials have reported a significant benefit for chemotherapy-treated patients. Because most relapses occur locally, post-operative adjuvant chemoradiotherapy was studied in patients who received surgery alone or surgery followed by 5-fluorouracil and leucovorin (5-FU/LV, Mayo Clinic regimen) given before, after, and concurrently with radiotherapy in the Intergroup 0116 trial. The 3-year survival and 3-year disease-free survival rates were significantly higher in the adjuvant treatment group, making this regimen the adjuvant standard in the United States. A second trial, the MAGIC trial, also showed improved survival and disease-free survival with epirubicin, cisplatin, and 5-FU (ECF) given every 3 weeks pre- and post-operatively. Other agents in combination with perioperative radiotherapy and surgery are being investigated to treat patients with gastric cancer. New target-oriented agents, as well as tailored therapy based on the molecular profile of both the tumor and the patient, might also contribute to improved results.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fluorouracil; Gastrectomy; Humans; Leucovorin; Radiotherapy, Adjuvant; Stomach Neoplasms

LV (l-LV)/5-FU therapy has been used broadly and is considered to be a standard treatment for large bowel cancer due to an enhancing therapeutic effect of 5-FU. According to recent clinical study reports on large bowel cancer in Europe and the United States, various administration methods of LV/5-FU with a combination of other drugs have been devised. It appeared that 5-FU used together in bolus and continuous infusions have yielded outstanding results. Although the basis of combination therapy for gastric cancer seemed to be LV/5-FU, there were many reports on TS-1 combined with other drugs because the oral medicine TS-1 was domestically available for the past one or two years. Currently, controlled randomized trials of LV/5-FU therapy and TS-1 have been ongoing. However, when patients cannot take oral intakes, LV/5-FU therapy is important. It seems that LV/5-FU therapy in combination with other drugs, in particular, CDDP, CPT-11, paclitaxel, docetaxel, oxaliplatin, and ETP will be given as candidates for the standard treatment of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Survival Rate

The effectiveness of chemotherapy for metastatic gastric cancer has been already revealed. But a standard chemotherapy has not been established yet. New agents such as TS-1, CPT-11 and taxanes are improving the response rates and also the survivals for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard resume will be sent abroad. In this article, we described the current state of CPT-11 combined chemotherapy for gastric cancer. Among various CPT-11- combined chemotherapy, CPT-11 + TS-1 is the most effective and less toxic treatment.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Mitomycin; Oxonic Acid; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

Following the successful introduction of oxaliplatin into the management of advanced colorectal cancer, its clinical utility is currently being investigated in a variety of other malignancies, including cancers of the upper gastrointestinal tract. In advanced pancreatic cancer, oxaliplatin has been found to be clinically effective in phase II trials in which it was combined with either 5-fluorouracil (5-FU) or gemcitabine, the current standard chemotherapy for this disease. In a phase II trial involving 67 patients, the combination of oxaliplatin and 5-FU in a high dose infusional regimen (n = 31) achieved an objective response rate of 9.7%, stable disease for at least three cycles in 48.4% of patients, tumour growth control in 58% of patients, a median time to progression of 4.9 months and median overall survival reaching 9.2 months. In combination with gemcitabine in a phase II trial involving 64 patients with metastatic (n = 34) or locally advanced (n = 30) pancreatic cancer, there was an objective response rate of 30.6%, treatment benefit in 39.7%, a median progression-free survival of 5.3 months and again a median overall survival of 9.2 months. Response rates and survival times did not differ between locally advanced and metastatic disease. On the basis of these encouraging results, phase III studies of oxaliplatin in advanced pancreatic cancer are now in progress in Europe and the United States. In metastatic gastric cancer, a phase II study investigated the combined use of oxaliplatin and 5-FU using the FOLFOX6 regimen in 53 patients, of whom 49 were evaluable for efficacy. The objective response rate was 44.9% and the median duration of response was 7.9 months. Large phase III trials of oxaliplatin-based treatment for advanced gastric cancer are now in progress. Oxaliplatin is also being investigated in oesophageal cancer and several other gastrointestinal tumours. In summary, oxaliplatin is emerging as an effective and highly promising chemotherapeutic agent for the treatment of upper gastrointestinal malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease Progression; Esophageal Neoplasms; Fluorouracil; Gemcitabine; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Stomach Neoplasms; Survival Rate

In the treatment of gastric cancer R0 surgical resection is the only hope for cure. Unfortunately most patients are first seen when they are in an advanced stage, when the possibility of R0 resection is very poor. In these cases administration of other therapies is justified. In the last decade neoadjuvant combination chemotherapy had been introduced with promising results. ECF neoadjuvant chemotherapy has 60% response rate in irresectable cases. We report about a patient with locally advanced gastric cancer treated with neoadjuvant ECF chemotherapy. The patient reacted with complete response, so following chemotherapy R0 resection could be carried out. We describe different therapies used for patients with locally advanced gastric cancer. Neoadjuvant chemotherapy is a recommended therapeutic modality in locally advanced gastric cancer, because it may have the effect of irresectable disease becoming resectable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Epirubicin; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Remission Induction; Stomach Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Randomized Controlled Trials as Topic; Stomach Neoplasms; Treatment Outcome

Levofolinate and fluorouracil regimen (l-leucovorin and 5 fluorouracil regimen) is a biochemical modulation of 5 fluorouracil (5FU) by leucovorin (LV). In the USA and Europe d,l-LV and 5FU regimen is frequently administered for colorectal cancer treatment and recognized as the standard regimen. In Japan, multi-institutional clinical trials of l-leucovorin (l-LV), a bioactive diastereomer of leucovorin, and 5FU combination were conducted for the treatment of advanced gastrointestinal cancer with comparable results to the US/Europe data. This l-LV and 5FU regimen was approved in August 1999 for the indications of advanced gastric cancer and colorectal cancer. The dosage and administration is referred to the weekly method developed at RPMI. Recently, the irinotecan (CPT-11) or oxariplatin plus LV and 5FU combination showed higher antitumor activities than the LV and 5FU combination with increased progression-free survival. These regimens, however, are not yet properly established because clinical trial results with Japanese patients are not completed for agreement of the dosage and administration schedule. For the l-LV and 5FU regimen diarrhea and leukocytopenia, including grade 3 and higher, were reported as the major adverse events. Administration for eligible patients with periodical monitoring of diagnostic data is necessary.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Treatment Outcome

Recently, cisplation (CDDP) and CPT-11 have joined the other drugs used for gastrointestinal chemotherapy, and the combination of I-leucovorin (I-LV)/5-FU has become available for use in medical treatment in Japan. This enables doctors to make a variety of regimens for gastrointestinal cancers. In this paper, we explain the new combinations, especially LV/5-FU/platinum, CPT-11/CDDP, and LV/5-FU/CPT-11. The combination of 5-FU/LV/CPT-11 has shown a higher antitumor activity than 5-FU/LV alone, with increased progression free survival or time-to-treatment failure. This combination will be considered the new standard regimen for colorectal cancer. It is worthy of note that the combination of UFT/LV provided on equally effective but safe and more convenient oral alternative to the standard i.v. 5-FU/LV regimen for colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colorectal Neoplasms; Docetaxel; Fluorouracil; Humans; Irinotecan; Leucovorin; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Analysis; Taxoids

Whether gastric cancer in young adults differs from gastric cancer in older patients has been a controversial issue. It has long been suspected that young patients with gastric cancer have different biological features with a more aggressive course of disease and a poorer prognosis than older patients. This, however, has not been firmly substantiated. We report on the clinical course of four patients (three female and one male) with locally advanced (n = 1) or metastasized (n = 3) non-resectable gastric cancer diagnosed under the age of 29 years (23, 25, 27, 28 years). Prior to diagnosis, all three women had recently been pregnant (1-22 months). Diagnosis was endoscopically biopsy-proven and staging work-up was performed by primary explorative surgery (n = 1), laparoscopy and explorative surgery (n = 1) or CAT scan and ultrasound (n = 2). The delay between initial symptoms and diagnosis was 8-22 weeks (median, 10 weeks). The histology was signet-ring cell (n = 2) or undifferentiated (n = 2) gastric cancer. All patients had the diffuse type of gastric cancer according to Lauren. Patients were treated with the FLAP polychemotherapy regimen consisting of leucovorin, 5-fluorouracil, doxorubicin and cisplatinum, as previously reported. The best response after chemotherapy was partial in two patients. Two patients showed progressive disease. Secondary surgery was performed in three responding patients (one of them responded only locally). One patient achieved no evidence of disease after complete tumor resection (R0). In two patients surgery was palliative (R2/exploration). Three patients died 6, 4 and 8 months after diagnosis. One patient is still alive. In our series, very young adults with gastric cancer had adverse clinical and pathological features. In accordance with other reports, we observed a predominance of female patients and a possible association with recent pregnancies. Though the delay between the first symptoms and diagnosis in our patients was no different from that reported for older patients, special emphasis should be given to prompt referral and diagnostic investigations, ensuring the diagnosis of gastric cancer early in the course of disease.

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Doxorubicin; Female; Floxuridine; Helicobacter pylori; Humans; Leucovorin; Male; Pregnancy; Pregnancy Complications, Neoplastic; Preoperative Care; Stomach Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Epirubicin; Etoposide; Fluorouracil; Humans; Leucovorin; Methotrexate; Randomized Controlled Trials as Topic; Stomach Neoplasms

5-FU is an important anticancer agent for many tumor entities. Because of the historical development of this compound it was predominantly administered as a bolus application, although it was well known that the antineoplastic activity of this antimetabolite is improved by prolonged administration schedules (protracted infusion ["infusional"] of 5-FU). Since port-a-cath systems and portable pumps became available, "infusional" 5-FU containing chemotherapies were intensively investigated in various tumors known to be susceptible to 5-FU.. The largest experience with "infusional" 5-FU +/- folinic acid +/- other cytostatic drugs exists in gastrointestinal tumors. Meanwhile this way of 5-FU application is well established in the first- and second-line chemotherapy of metastatic colorectal and gastric cancer where it contributes to a clinically relevant improvement of the prognosis of these tumors. Other tumor entities where "infusional" 5-FU-based chemotherapies showed first positive results are i.e. breast cancer and esophageal cancers.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Remission Induction; Stomach Neoplasms

Neoadjuvant chemotherapy for high-risk patients with advanced gastric cancer is important to increase the chance for curative resection and make unresectable gastric cancer tumors resectable by down-staging of the tumor. Tumors with H0, P0, T3, T4, or N3 are the best candidates for this therapy. Randomized controlled phase III studies are needed in conjunction with accurate staging of the disease by laparoscopy. The results of histopathologic evaluation of resected materials following preoperative chemotherapy using oral fluoropyrimidine are thought to be useful as an indicator of chemosensitivity for postoperative adjuvant setting.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Etoposide; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Preoperative Care; Stomach Neoplasms; Survival Rate

During the last 40 years, 5-fluorouracil 5-FU) has been the drug of choice for treatment of patients with gastrointestinal cancer. However, its effectiveness is far from satisfactory. It has been determined that leucovorin (LV) potentiates the cytotoxic effect of 5-FU through prolonged inhibition of thymidylate synthase. A series of 10 trials comparing LV.5-FU with 5-FU alone were reported. A significantly higher objective response rate was seen with LV.5-FU, but there was no increase in survival. In randomized trials comparing low-dose and high-dose LV as modulates of 5-FU in treating advanced colorectal cancer, high doses of LV presented no advantage over low doses. Adjuvant LV.5-FU was compared to surgery alone in large group trials, demonstrated and a statistically significant decrease in disease and increase in overall survival. These data suggest that LV.5-FU is a very effective combination and most clinicians worldwide now regard it as the standard therapy for colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Survival Rate

UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

Topics: Administration, Oral; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Combinations; Humans; Leucovorin; Lung Neoplasms; Neoplasms; Stomach Neoplasms; Tegafur; Uracil

"Second generation" combination chemotherapy regimens were developed in the 1980s with high activity in locally advanced and metastatic disease. Among them were etoposide plus doxorubicin plus cisplatin (EAP), etoposide plus 5-fluorouracil plus leucovorin (ELF), continuous infusion of 5-fluorouracil plus cisplatin (FP) and high-dose methotrexate plus S-fluorouracil plus doxorubicin (FAMTX). In locally advanced disease a resectability rate of +/- 50% was reported with these protocols. FAMTX was felt to be superior to 5-fluorouracil, doxorubicin and mitomycin (FAM), which regimen had been considered "standard" treatment for many years. Randomized studies, however, did not reveal significant differences among various second generation regimens. Future studies should focus on innovative protocols in advanced disease, the role of neoadjuvant chemotherapy in clinically staged locally advanced disease, the role of local "consolidation treatment," ie, radiotherapy or intraperitoneal chemotherapy after primary chemotherapy plus resection, and preoperative and postoperative chemotherapy in operable disease.

Topics: Antibiotics, Antineoplastic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Etoposide; Fluorouracil; Gastrectomy; Humans; Leucovorin; Methotrexate; Mitomycins; Randomized Controlled Trials as Topic; Stomach Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Humans; Leucovorin; Liver Neoplasms; Lymphoma, B-Cell; Male; Methotrexate; Neoplasm Invasiveness; Pancreatic Neoplasms; Prednisone; Remission Induction; Retroperitoneal Neoplasms; Stomach Neoplasms; Vincristine

The biomodulation (BM) of 5-fluorouracil (5-FU) by interferon (IFN) is reviewed both preclinically and clinically, stressing clinical relevance. A number of preclinical evaluations of a combination of 5-FU and IFN were performed before Wadler et al. developed an active biomodulation therapy with a combination of 5-FU and IFN. However, extensive preclinical investigations have been performed very recently showing that IFN can enhance cytotoxic effects of 5-FU through various mechanisms, not only by increased anabolism of 5-FU to 5-fluoro 2'-deoxyuridine monophosphate (FdUMP) or 5-fluorouridine (FUR), inhibition of thymidine kinase activity, possible alternation of pharmacokinetics of 5-FU, but also by biological response modification. Since a high response rate of 76.4% in patients with previously untreated advanced metastatic colorectal cancer was reported by Wadler et al., with the combination of 5-FU and IFN, consecutive extensive phase II studies of the combination have been undertaken and shown a modest response rate ranging from 25% to 43% for colorectal cancer. An attempt to add leucovorin (LV) to the combination of 5-FU and IFN has so far appeared less successful. It showed almost the same efficacy in terms of response rate and survival, but more significant side effects. A further study is warranted to evaluate the optimal dose and schedule of IFN in combination with 5-FU or the 5-FU and LV combination chemotherapy in the proper sense of biomodulation. The role of biomodulating chemotherapy of 5-FU by IFN or IFN and LV must also be investigated in the field of head and neck cancers, esophageal cancer, biliary tract cancer, all of which are relatively sensitive to the effector of 5-FU.

Topics: Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Recombinant Proteins; Stomach Neoplasms

The main purpose of this trial was to investigate the activity of a less toxic regimen in patients with advanced gastric carcinoma regarding response rate and survival. We report on a pilot study of 20 patients treated with the combination of 5-fluorouracil and folinic acid. 5-fluorouracil was administered at a daily dose of 450 mg/m2 followed by folinic acid 200 mg/m2 for four consecutive days every four weeks. The overall response rate was 15% with one complete and two partial responders. The median duration of response was 11, 10 and 10 months respectively. The median survival of all patients was 9 months. Toxicity was mild and consisted primarily of diarrhea. Stomatitis and myelosuppression occurred rarely. In conclusion, the combination of 5-fluorouracil and folinic acid has moderate activity in gastric cancer, while median survival appears similar to the other more intensive regimens. The combination is very well tolerated with minimal toxicity. A detailed review of the literature regarding the effectiveness of the above regimens on response rate, overall survival and toxicity is also presented.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Stomach Neoplasms

Cancer chemotherapy plays a central role in the treatment of recurrent or unresectable scirrhous gastric cancers classified mainly as Borrmann type 4. Though we have no specifically effective drugs for scirrhous gastric cancer, 5-FU and its derivative, MMC, anthracyclines, CDDP, CQ and ACNU are known to be relatively effective single agents against this tumor. In an attempt to enhance the effect of single agents, several combined chemotherapy regimens have been devised and tested. These regimens included 5-FU + MMC, UFT + MMC, UFT + CDDP, MTX.5-FU, FAM, FAP, EAP and ELF regimen. At present, combined therapies using 5-FU and MTX or CDDP may be the most attractive of these combined regimens.

Topics: Adenocarcinoma, Scirrhous; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Etoposide; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Levoleucovorin; Mitomycin; Nimustine; Recombinant Proteins; Stomach Neoplasms; Tegafur; Uracil

5-Fluorouracil (5-FU) is one of the important antineoplastic agents for the treatment of gastrointestinal cancers. The biochemical modulation of 5-FU by various drugs has brought about the two combinations of 5-FU/folinic acid (FA) and 5-FU/alpha-interferon (IFN), which have shown clinical activity in phase II and III trials, especially in colorectal cancer. The experience with both combinations in upper gastrointestinal cancers, however, is limited. In esophageal cancer, two phase II studies with 5-FU/IFN reported seven (27%) objective remissions in 26 patients, indicating superiority of 5-FU/IFN over 5-FU monotherapy. Trials with 5-FU/FA alone are lacking in esophageal cancer. The modulation of 5-FU by IFN or FA failed to show clinically significant activity in pancreatic cancer. However, in gastric cancer, 5-FU/FA and 5-FU/IFN seem to induce higher complete and overall remission rates in advanced gastric cancer compared with 5-FU alone. With the daily times five schedule of 5-FU/FA, 27% objective remissions were achieved; in combination with other cytotoxic drugs, such as etoposide, anthracyclines, cisplatin, mitomycin, or methotrexate, objective response rates up to 50% and more were reported.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Pancreatic Neoplasms; Stomach Neoplasms

Biochemical modulation is a word to mean biochemical or pharmacological modulation of the efficacy or side effects of a anticancer drug. Historically, combination therapy of methotrexate (MTX) and 5-fluorouracil (5-FU) developed by Bertino et al. in 1970s has been proved to be effective to advanced gastric cancer. Many combination therapies from 1960s seem to be based on this concept of biochemical modulation. Beside MTX and 5-FU combination, currently combined use of 5-FU or other fluoropyrimidines with cisplatin (CDDP) has been studied for the treatment of cancer of the digestive organs. The therapeutic efficacies in these combination of drugs were also found to be based on biochemical or pharmacological modulation of anticancer drugs.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Methotrexate; Stomach Neoplasms

Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l-LV schedule against gastric cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Evaluation; Fluorodeoxyuridylate; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Thymidylate Synthase

Combination chemotherapy for advanced gastrointestinal malignancies remains unsatisfactory. Studies show a definite therapeutic advantage for folinic acid/5-fluorouracil (5-FU) regimen compared with single agent 5-FU given intravenously in the management of advanced colorectal cancer. Data on survival benefits vary. A definitive conclusion regarding this question must outweigh the maturation of the present studies and possibly generate further extensive investigations. The currently available data are insufficient from which to draw any conclusion on the effect of the attempt to modulate 5-FU activity further by the addition of cisplatin to the combination. Nevertheless, the combination appears to elicit some therapeutic advantage in patients with pancreatic carcinoma and rectal carcinoma. The paucity of data in gastric carcinoma is disappointing in light of sensitivity to both cisplatin and 5-FU.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Drug Evaluation; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Meta-Analysis as Topic; Pancreatic Neoplasms; Stomach Neoplasms

Many clinical trials with 5-fluorouracil and leucovorin have been reported. This combination therapy seems to play an important role in untreated advanced colorectal cancer. In other neoplasms (gastric, head and neck, breast cancer) further studies are required.

Topics: Adenocarcinoma; Breast Neoplasms; Colorectal Neoplasms; Drug Evaluation; Drug Therapy, Combination; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Meta-Analysis as Topic; Stomach Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms

The biochemical modulation of 5-fluorouracil (FU) by using it in combination with leucovorin (LV) is reviewed. One of the mechanisms of action of FU is inhibition of thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate required for DNA repair and synthesis. In the presence of 5, 10-methylene tetrahydrofolate, 5-fluoro-deoxyuridine monophosphate (FdUMP), which is an active nucleotide of FU, forms a ternary complex with TS, resulting in enzyme inhibition. The rationale for the use of LV with FU is to increase of formation and stability of catalytically inactive ternary complexes. In clinical trials, the dose schedules of 500 mg/m2 iv bolus or 500 mg/m2 continuously iv infusion is frequently used in order to obtain an ideal plasma concentration of active LV metabolites. Preliminary clinical trials using the combination of FU and LV appear to be capable of increasing of the clinical activity of FU for colorectal and breast cancers. Several randomized studies have supported the increase in response rates seen in the uncontrolled trials but additional studies are required to demonstrate a positive impact on the survival of treated patients.

Topics: Chemical Phenomena; Chemistry; Drug Evaluation; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Neoplasms; Stomach Neoplasms

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Ramucirumab; Stomach Neoplasms; Vascular Endothelial Growth Factor A

Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI.. In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death.. Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS).. GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Randomized Controlled Trials as Topic; Stomach Neoplasms; Treatment Outcome

Perioperative chemotherapy is a potential treatment for locally advanced gastric cancer. However, the optimal chemotherapy regimen remains unknown.. To investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) vs fluorouracil, leucovorin, and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced gastric cancer.. In this phase 3, open-label, multicenter, randomized clinical trial, patients from 12 Chinese hospitals were enrolled between June 2011 and August 2016, with a last follow-up date of September 2019. The primary tumor was evaluated as either invading the serosa or the adjacent structures with or without metastatic lymph nodes, and with no evidence of distant metastases. Data were analyzed from December 2019 to June 2020.. Patients were randomly assigned (1:1) to receive either 6 perioperative (2-4 preoperative and 2-4 postoperative) 3-week cycles of 130 mg/m2 oxaliplatin on day 1 and 80 to 120 mg/d S-1 orally daily for 2 weeks (SOX) or 130 mg/m2 oxaliplatin, 400 mg/m2 fluorouracil, 400 mg/m2 leucovorin, and 2400 mg/m2 fluorouracil as 46-hour infusion on day 1 (FOLFOX).. The primary end point was 3-year overall survival (OS). An absolute noninferiority margin of -8% was chosen.. A total of 583 patients were enrolled; 293 were randomized to the SOX group and 290 were randomized to the FOLFOX group. Twelve patients (2.1%) refused preoperative chemotherapy (5 patients in the SOX group and 7 patients in the FOLFOX group), leaving a total of 288 patients in the SOX group (median [range] age, 61 [24 to 78] years; 197 men [68.4%]) and 283 patients in the FOLFOX group (median [range] age, 62 [24 to 80] years; 209 men [73.9%]) who received preoperative chemotherapy. The 3-year OS rate was 75.2% (95% CI, 70.3% to 80.5%) in the SOX group and 67.8% (95% CI, 62.5% to 73.5%) in the FOLFOX group. The absolute difference of 3-year OS rate between the 2 groups was 7.4% (95% CI, -0.1% to 14.9%), which was greater than the prespecified noninferiority margin (-8%) and showed the noninferiority of perioperative chemotherapy with SOX compared with FOLFOX.. In this randomized clinical trial, SOX was noninferior to FOLFOX as perioperative chemotherapy for patients with locally advanced gastric cancer and could be recommended as an alternative treatment for these patients in Asia.. ClinicalTrials.gov Identifier: NCT01364376.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Stomach Neoplasms

Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma.. GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4-6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4-10 weeks after surgery. Using a Simon's two-stage design, up to 67 patients will be enrolled, including 23 in the first stage.. Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes.. NCT04736485, registered February, 3, 2021.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Stomach Neoplasms; Tumor Microenvironment

The perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin plus docetaxel (FLOT) was recommended by the Chinese Society of Clinical Oncology Guidelines for gastric cancer (2018 edition) for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (class IIA). However, the economic impact of FLOT chemotherapy in China remains unclear. The analysis aimed to compare the cost-effectiveness of FLOT versus epirubicin, cisplatin plus fluorouracil or capecitabine (ECF/ECX) in patients with locally advanced resectable tumours.. We developed a Markov model to compare the healthcare and economic outcomes of FLOT and ECF/ECX in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Costs were estimated from the perspective of Chinese healthcare system. Clinical and utility inputs were derived from the FLOT4 phase II/III clinical trial and published literature. Sensitivity analyses were employed to assess the robustness of our result. The annual discount rate for costs and health outcomes was set at 5%.. The primary outcome of incremental cost-effectiveness ratios (ICERs) was calculated as the cost per quality-adjusted life years (QALYs).. The base-case analysis found that compared with ECF/ECX, the use of FLOT chemotherapy was associated with an additional 1.08 QALYs, resulting in an ICER of US$851/QALY. One-way sensitivity analysis results suggested that the HR of overall survival and progression-free survival had the greatest impact on the ICER. Probabilistic sensitivity analysis demonstrated that FLOT was more likely to be cost-effective compared with ECF/ECX at a willingness-to-pay threshold of US$31 513/QALY.. For patients with locally advanced resectable tumours, the FLOT chemotherapy is a cost-effective treatment option compared with ECF/ECX in China.. NCT01216644.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cost-Benefit Analysis; Docetaxel; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

Gastric or gastro-oesophageal junction (GEJ) adenocarcinomas present poor overall survival (OS). First-line chemotherapy regimen for patients with HER2-negative tumours is based on a doublet or triplet of fluoropyrimidine plus platinum salt ± taxane. Second-line chemotherapy (Docetaxel or Irinotecan) improves OS which nonetheless remains poor (around 5 months). The first results of immune checkpoint inhibitors (anti-PD-1) combined with chemotherapy in metastatic gastric and GEJ cancers were discordant in recent phase III trials. Data on dual-blockade (anti-PD-L1 or anti-PD-1 plus anti-CTLA-4) plus chemotherapy are lacking. DURIGAST is a randomised, multicenter, non-comparative, phase II study, evaluating safety and efficacy of FOLFIRI plus Durvalumab (anti-PD-L1) versus FOLFIRI plus Durvalumab and Tremelimumab (anti-CTLA-4) as second-line treatment of advanced gastric and GEJ adenocarcinoma. The primary objective is the rate of patients alive and without progression at 4 months. The main inclusion criteria are: patients with advanced gastric or GEJ adenocarcinoma, pre-treated with fluoropyrimidine + platinum salt ± taxane. Due to a lack of data on FOLFIRI, Durvalumab and Tremelimumab combination, a 2-step safety run-in phase has been performed before the randomised phase II. The safety run-in phase did not show any safety issue and the randomised phase II starts in September 2020.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; France; Humans; Leucovorin; Male; Stomach Neoplasms; Treatment Outcome

Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9, an extracellular enzyme involved in matrix remodeling, tumor growth, and metastases. A phase I and Ib study of modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) with ADX revealed encouraging antitumor activity in patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma.. This phase III, randomized, double-blinded, placebo (PBO)-controlled multicenter study investigated the efficacy and safety of mFOLFOX6 with and without ADX in patients with untreated human epidermal growth factor receptor 2-negative gastric or GEJ adenocarcinoma. Random assignment was 1:1 to mFOLFOX6 + ADX or mFOLFOX6 + PBO. ADX/PBO 800 mg was infused on days 1 and 15 of each 28-day cycle. Protocol therapy was given until disease progression or intolerance. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), objective response rate (RECIST 1.1), and safety.. Between September 2015 and May 2017, 432 patients were randomly assigned, 218 to ADX and 214 to PBO. The median OS was 12.5 versus 11.8 months in the ADX and PBO groups, respectively. The median PFS was 7.5 versus 7.1 months in the ADX and PBO groups, respectively. The objective response rate was 51% in the ADX group and 41% in the PBO group. Among the subgroup analyses, patients of age ≥ 65 years had an improved OS and PFS with ADX versus PBO; the. The addition of ADX to mFOLFOX6 did not improve OS in unselected patients with untreated human epidermal growth factor receptor 2-negative gastric or GEJ adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Prognosis; Stomach Neoplasms; Survival Rate; Young Adult

The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment.. To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk.. This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020.. Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1).. The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points.. A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase.. The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption.. ClinicalTrials.gov Identifier: NCT03674294.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Camptothecin; China; Double-Blind Method; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Nausea; Organoplatinum Compounds; Stomach Neoplasms; Vomiting

Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen.. The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled.. NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carcinoma, Neuroendocrine; Etoposide; Female; Fluorouracil; Humans; Intestinal Neoplasms; Irinotecan; Leucovorin; Male; Neoplasm Metastasis; Neoplasms, Unknown Primary; Neuroendocrine Tumors; Oxaliplatin; Pancreatic Neoplasms; Platinum Compounds; Progression-Free Survival; Prospective Studies; Quality of Life; Stomach Neoplasms; Survival Rate; Treatment Outcome

There is a lack of pharmacogenetic predictors of outcome in gastric cancer patients. The aim of this study was to assess previously identified candidate genes associated with 5-fluorouracil (5-FU), cisplatin, or epirubicin toxicity or response in a cohort of resected gastric cancer patients treated on CALGB (Alliance) 80101. Gastric or gastroesophageal cancer patients randomized to adjuvant 5-FU/leucovorin or epirubicin/cisplatin/5-FU before and after 5-FU chemoradiation were genotyped for single nucleotide polymorphisms (SNPs) in GSTP1 (rs1695), ERCC1 (rs11615 and rs3212986), XRCC1 (rs25487), UGT2B7 (rs7439366) and the 28 base-pair tandem repeats in TYMS (rs34743033). Logistic regression and log rank tests were used to assess the association between each SNP and incidence of grade 3/4 neutropenia and leukopenia, overall (OS) and progression-free survival (PFS), respectively. Toxicity endpoint analyses were adjusted for the treatment arm, while OS and PFS were also adjusted for performance status, sex, age, lymph node involvement, and primary tumor site and size. Of 281 subjects with successful genotyping results and available clinical (toxicity and efficacy) data, 166 self-reported non-Hispanic White patients were included in the final analysis. There was a lack of evidence of an association among any SNPs tested with grade 3/4 neutropenia and leukopenia or OS and PFS. Age, lymph node involvement, and primary tumor size were significantly associated with OS and PFS. This study failed to confirm results of previous gastric cancer pharmacogenetic studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Fluorouracil; Humans; Leucovorin; Pharmacogenomic Testing; Stomach Neoplasms; X-ray Repair Cross Complementing Protein 1

Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor. It is synergistic with chemotherapy in preclinical models. We hypothesized that sunitinib in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) would be a tolerable and effective regimen in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.. Since the outcomes of advanced gastric and GEJ adenocarcinoma patients are poor, we decided to study a combination of FOLFIRI + S, to establish tolerability and efficacy.. This was a phase I study for patients with advanced chemo-naïve gastric or GEJ adenocarcinoma. Dose escalation used a standard 3 + 3 design. The primary objective was to determine the tolerability and safety of FOLFIRI + S. Secondary objectives were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).. A total of 23 patients participated in the study (male 78%, female 22%). The median age was 61 (range: 38-77) years. Median follow-up time was 67.5 (95% CI 58.9-76) months. The most frequently reported adverse events were anemia (78%; G3/4: 4%), neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%), and fatigue (52%; G3/4:17%). Two dose-limiting toxicities were noted each at dose level (DL) 1 and 1A, one at DL 1B, and three at DL 2. Maximum tolerated dose was determined at DL 1B. At the time of data reporting, 21 patients had died. The median OS and PFS were 12.4 (95% CI 8.9, 16.5) months and 6.2 (95% CI 3.4, 13.5) months, respectively. Of all patients, 35% (eight out of 23) had a partial response.. FOLFIRI + S has signs of clinical activity in patients with advanced gastric and GEJ adenocarcinoma, and the side-effect profile was similar to previously reported studies. Current treatment paradigms in gastric cancer probably negate further study of this regimen. ClinicalTrials.gov identifier: NCT00524186.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Progression-Free Survival; Stomach Neoplasms; Sunitinib

Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral. Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of. Eighty-six percent of patients had. The evaluation of

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Endonucleases; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Gene Expression; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Prognosis; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Stomach Neoplasms; Young Adult

Using data from the 4-year follow-up results of an open, randomised, phase II study, this patient-based cost-effectiveness analysis compares mFOLFIRI (irinotecan, 5-fluorouracil and leucovorin, the IRI arm) with mFOLFOX7 (oxaliplatin, 5-fluorouracil and leucovorin, the OXA arm) as first-line treatments in patients with locally advanced gastric adenocarcinoma (GC).. A Markov model was created based on previous results reported at the 2016 Gastrointestinal Cancers Symposium to evaluate mFOLFIRI and mFOLFOX7 for advanced GC quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were examined as the primary outcomes.. For the evaluable 128 patients, treatment efficacy was 0.59 QALYs for the IRI arm and 0.70 QALYs for the OXA arm, with a total cost of $13,861.34 for the IRI arm and $14,127.30 for the OXA arm. Hence, the ICER was $2,417.82 per QALY the OXA arm, which was below the threshold of 3 × per capita GDP of China. For subgroup analysis of those receiving mFOLFIRI followed by mFOLFOX7 (the IRI arm) and the reverse (the OXA arm), the OXA arm gained 0.44 more QALYs than the IRI arm with a total cost of $28,890.09 for the IRI arm and $31,147.30 for the OXA arm. However, the cost per QALY was also lower for the OXA arm than for the IRI arm, and the cost per QALY gained was $5,129.55 (below the Chinese WTP).. mFOLFOX7 is a very high cost-effective alternative as the first-line treatment for those patients with advanced GC compared with mFOLFIRI.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; China; Cost-Benefit Analysis; Female; Fluorouracil; Humans; Leucovorin; Male; Markov Chains; Middle Aged; Organoplatinum Compounds; Quality-Adjusted Life Years; Stomach Neoplasms; Treatment Outcome; Young Adult

Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l-leucovorin (l-LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/l-LV.. Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20-75 years; performance status (PS) 0-2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/l-LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949.. We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/l-LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596-1.053; one-sided p = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43-0.96; p = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/l-LV arm. In the 5-FU/l-LV arm, two deaths were treatment-related. In the 5-FU/l-LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively.. Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate

Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value.. To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma.. This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019.. Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg).. Margin-negative resection rate and PRG.. A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]).. In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients.. ClinicalTrials.gov Identifier: NCT02366819.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Female; Fluorouracil; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Oxaliplatin; Positron-Emission Tomography; Stomach Neoplasms

Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma. Similarly, irinotecan-based therapy has marginal efficacy. We combined irinotecan plus a fluoropyrimidine with an anti-PD-1 antibody, nivolumab, with hopes of having a higher advantage for patients.. Primary objective was to assess safety judged by toxicities, dose delays, or dose reductions. Secondary endpoints included the assessment of response, overall survival (OS), and progression-free survival (PFS).. We treated 15 patients with this combination during July 2017 to April 2019. Patients were included if they had follow-up at our institution.. Median doses given were nivolumab 240 mg + irinotecan 120 mg/m2 + 5-FU 2,000 mg/m2 over 46-48 h (or capecitabine 1,250 mg/m2/day; 7 days on, 7 days off) given every 2 weeks. Median age of the patients was 55 years, and all patients had an ECOG performance status of 0-1. The patients had a median of 1 prior therapy. Slightly over half of the patients had PD-L1 expression. The median number of cycles was 7. Five patients (33%) had a dose delay or dose adjustment. The most common reason for dose delay or adjustment was grade 2 fatigue. Disease control (response or stability) on first scan was 73.3% (n = 11). Median PFS and OS for the entire group was 7 and 13.3 months, respectively.. In this small cohort of patients, we conclude that this combination is quite feasible and resulted in prolonged stability in some patients. Further development of this regimen is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nivolumab; Prognosis; Progression-Free Survival; Retrospective Studies; Stomach Neoplasms

In patients with advanced gastric cancer refractory to chemotherapy, the treatment options are limited. Via this phase II study, we aimed to assess the efficacy and safety of oxaliplatin in combination with 5-fluorouracil and l-leucovorin (modified FOLFOX6).. Patients who had histologically confirmed metastatic gastric cancer refractory to ≥ two previous chemotherapy regimens were included. The primary endpoint was the overall response rate (ORR) by an independent central review. According to an assumption of a threshold ORR of 10% and expected ORR of 25%, with α = 0.05 and β = 0.20, at least 33 patients were required. The secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life measured by EQ-5D, and safety.. Among the 35 enrolled patients, 33 were included in the primary analysis. All patients previously received fluoropyrimidines, cisplatin, and taxanes, and 24 (73%) were pretreated with irinotecan. The confirmed ORR was 27% [95% confidence interval (CI) 13-46]. The median PFS and OS were 2.2 (95% CI 1.2-3.2) and 5.6 (95% CI 4.1-7.0) months, respectively. In the multivariate analyses, immunotherapy within 90 days and a Glasgow Prognostic Score of 0 were associated with better treatment outcomes. The most common grade ≥ 3 adverse event was neutropenia (36%), and no febrile neutropenia was observed. The median EQ-5D scores did not change from baseline at 2, 4, and 8 weeks (p value = 0.38, 0.79, and 0.98, respectively).. Modified FOLFOX6 (mFOLFOX6) showed substantial activity and acceptable toxicity for chemotherapy-refractory advanced gastric cancer.. UMIN Clinical Trial Registry (UMIN000016416).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Progression-Free Survival; Stomach Neoplasms; Treatment Outcome

Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers.. To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma.. This is an open-label, single-arm phase 2 study of first-line FOLFIRINOX in patients with advanced gastroesophageal adenocarcinoma. Estimated sample size included 41 patients with ERBB2-negative disease with 90% power to detect an ORR of 60% or greater with α of .10. No enrollment goal was planned for ERBB2-positive patients, but they were allowed to receive trastuzumab in combination with FOLFIRINOX.. Starting doses were fluorouracil, 400 mg/m2 bolus, followed by 2400 mg/m2 over 46 hours; leucovorin, 400 mg/m2; irinotecan, 180 mg/m2; and oxaliplatin, 85 mg/m2. Trastuzumab was administered as a 6 mg/kg loading dose, followed by 4 mg/kg every 14 days in patients with ERBB2-positive disease.. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS), and duration of response.. From November 2013 to May 2018, 67 patients were enrolled (median [range] age, 59.0 [34-78] years; including 56 [84%] men), and 26 of 67 (39%) had ERBB2-positive disease. Median follow-up was 17.4 months. The ORR was 61%(95% CI, 44.5%-75.8%) (25 of 41) in the ERBB2-negative group and 85% (95% CI, 65.1%-95.6%) (22 of 26) in the ERBB2-positive group, including 1 patient with complete response. For ERBB2-negative patients, median PFS was 8.4 months and median OS was 15.5 months; for ERBB2-positive patients, median PFS was 13.8 months and median OS was 19.6 months. Fifty-six patients (84%) had dose modifications or treatment delays. The most common toxic effects were neutropenia (91%, n = 61), diarrhea (63%, n = 42), peripheral sensory neuropathy (61%, n = 41), and nausea (48%, n = 32), with no unexpected toxic effects.. The FOLFIRINOX regimen with or without trastuzumab was associated with improved ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status.. ClinicalTrials.gov Identifier: NCT01928290.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Oxaliplatin; Peripheral Nervous System Diseases; Stomach Neoplasms; Trastuzumab; Treatment Outcome

Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with a doublet chemotherapy consisting of a platinum compound and a fluoropyrimidine in combination with trastuzumab for HER2-positive disease or in selected cases with docetaxel, survival remains poor. Recently, immune-oncology based strategies relevantly improved the treatment of different solid tumors and showed some promise in late or later stage trials in EGA. Notably, the combination of immunotherapy with trastuzumab to enhance anti-tumor immunity through activation of innate and adaptive immunity was beneficial in preclinical studies or clinical studies in breast cancer.. The INTEGA study is an open-label, randomized, multicenter, exploratory phase II trial designed to assess clinical performance, safety and tolerability of ipilimumab or 5-FU/folinic acid and oxaliplatin (FOLFOX) in combination with nivolumab and trastuzumab in patients with previously untreated HER2-positive, locally advanced or metastatic EGA. The primary objective is to determine the clinical performance of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in terms of overall survival. Secondary objectives are safety and tolerability, efficacy in terms of progression-free survival and objective response rate and blood-based signatures (e.g. immune response or suppression of anti-HER2 resistance) that may correlate with treatment response.. Recent evidence from the phase II NCT02954536 study (oxaliplatin, capecitabine, trastuzumab and pembrolizumab) suggests the clinical feasibility of combining chemotherapy, trastuzumab and checkpoint inhibition in EGA. However, evidence for a chemotherapy-free regimen is also mounting in HER2-positive disease (NCT02689284) i.e. margetuximab and Pembrolizumab. Both studies excelled with high overall response rates and manageable toxicities. The INTEGA study aims to comparatively assess these results and select a promising new 1st line regimen which then needs to be confirmed in a randomized phase III trial. Further, the translational part of the study might help to better stratify patients and tailor treatment of either arm.. NCT03409848 24.01.2018.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Ipilimumab; Leucovorin; Male; Middle Aged; Multicenter Studies as Topic; Nivolumab; Organoplatinum Compounds; Progression-Free Survival; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Stomach Neoplasms; Trastuzumab

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; China; Docetaxel; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Morbidity; Neoadjuvant Therapy; Oxaliplatin; Patients; Postoperative Complications; Stomach; Stomach Neoplasms; Treatment Outcome

The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Prognosis; Stomach Neoplasms; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein

The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2.. In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model.. Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm. Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Epirubicin; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate

Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC.. In this randomised, double-blind, placebo-controlled, multicentre, phase II trial, patients with locally advanced or metastatic GC/GEJC not amenable to curative therapy were randomised 1:1 to receive ipatasertib or placebo, plus mFOLFOX6 (modified regimen of leucovorin, bolus and infusional 5-fluorouracil [5-FU], and oxaliplatin). The co-primary end-point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in phosphatase and tensin homolog (PTEN)-low patients. Secondary end-points included PFS in patients with PI3K/Akt pathway-activated tumours; overall survival, investigator-assessed objective response rate and duration of response in the ITT population; and safety assessments.. In 153 enrolled patients, the median PFS (ITT) was 6.6 months (90% confidence interval [CI], 5.7-7.5) with ipatasertib/mFOLFOX6 versus 7.5 months (90% CI, 6.2-8.1) with placebo/mFOLFOX6 (hazard ratio, 1.12; 90% CI, 0.81-1.55; P = 0.56). No statistically significant PFS benefit was observed in biomarker-selected patient subgroups (PTEN-low and PI3K/Akt pathway-activated tumours) with ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6. Other secondary end-points did not favour the ipatasertib/mFOLFOX6 treatment arm. The percentages of patients with ≥1 adverse event (AE, 100% versus 98%) and grade ≥3 AEs (79% versus 74%) were similar between arms. Higher rates of AEs leading to treatment withdrawal (16% versus 6%) and serious AEs were reported in the ipatasertib arm (54% versus 43%). Thirty-nine and 29 deaths occurred in the ipatasertib and placebo arms, respectively.. Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed.. ClinicalTrials.gov (NCT01896531).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Organoplatinum Compounds; Piperazines; Progression-Free Survival; Proto-Oncogene Proteins c-akt; Pyrimidines; Stomach Neoplasms

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1-2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1-2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42-74), and the median overall survival was 117 days (95% CI: 94-154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Prognosis; Ramucirumab; Stomach Neoplasms; Survival Rate

Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv-aflibercept, could improve the efficacy of first-line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5- fluorouracil) in metastatic esophagogastric adenocarcinoma.. Patients with treatment-naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo-controlled, double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept (4 mg/kg) every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS).. Sixty-four patients were randomized to receive mFOLFOX6 and ziv-aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6/ziv-aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (P = .06). The relative dose intensity of oxaliplatin and 5-fluorouracil was lower in the mFOLFOX6/ziv-aflibercept arm during the first 12 and 24 weeks of the trial. There were 2 treatment-related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6/ziv-aflibercept cohort.. Ziv-aflibercept did not increase the anti-tumor activity of first-line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv-aflibercept in unselected, chemotherapy-naive patients with metastatic esophagogastric adenocarcinoma is not warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Stomach Neoplasms; Survival Rate

Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase III study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Clinical Protocols; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Gene Amplification; Humans; Leucovorin; Male; Organoplatinum Compounds; Receptor, Fibroblast Growth Factor, Type 2; Research Design; Stomach Neoplasms

Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.. PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC.. The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy.. A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response.. The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoma, Neuroendocrine; Drug Administration Schedule; Female; Fluorouracil; France; Humans; Intestinal Neoplasms; Leucovorin; Male; Neuroendocrine Tumors; Pancreatic Neoplasms; Research Design; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer.. Patients enrolled in the SUN-CASE study received sunitinib or placebo as an adjunct to standard therapy with leucovorin (Ca-folinate), 5-fluorouracil, and irinotecan in second or third line. Treatment response rates, progression-free survival and overall survival were assessed during a follow-up period of 12 months. Cytokeratin-18 fragments were analyzed in 52 patients at baseline and day 14 of therapy.. Levels of M30 correlated with the presence of metastasis and lymph node involvement and decreased significantly during chemotherapy. Importantly, baseline levels of M30 were significantly higher in patients who failed therapy. In addition, patients who did not respond to treatment were also identifiable at day 14 based on elevated M30 levels. By stepwise regression analysis, M30 at day 14 was identified as independent predictor of treatment response. Likewise, serum levels of full-length cytokeratin-18 M65 at baseline also correlated with treatment failure and progression-free survival. The addition of sunitinib did not exert any effects on serum levels of M30 or M65.. The cytokeratin-18 fragment M30 at day 14 identifies patients that fail to second- or third-line therapy for advanced gastric cancer. Validation of this non-invasive biomarker in gastric cancer is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Disease-Free Survival; Female; Fluorouracil; Humans; Indoles; Keratin-18; Leucovorin; Male; Middle Aged; Peptide Fragments; Placebos; Pyrroles; Stomach Neoplasms; Sunitinib

Although nivolumab showed survival benefit in patients with advanced gastric cancer (AGC) progressing after standard chemotherapy, there is a lack of data regarding oxaliplatin-based chemotherapy in this clinical setting.. We retrospectively evaluated the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil as salvage treatment in patients with AGC refractory or intolerant to fluoropyrimidines, cisplatin, taxanes, and irinotecan.. Overall, 50 patients treated between December 2009 and December 2013 were included in this analysis. The overall response rate (ORR) was 21.2% among 33 patients with measurable disease. The median time to treatment failure (TTF) and overall survival (OS) were 2.4 and 4.2 months. In multivariate analysis, factors associated with OS included poor performance status [hazard ratio (HR) 3.20; 95% confidence interval (CI) 1.55-6.60], shorter time from the start of first-line therapy (HR 2.20; 95% CI 1.18-4.12), and higher neutrophil/lymphocyte ratio value (HR 4.87; 95% CI 2.32-10.25). In patients (n = 35) with at most one risk factor, the ORR, median TTF, and OS were 26.1%, 3.6, and 6.7 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (30%), anemia (22%), febrile neutropenia (8%), and peripheral neuropathy (8%). Initial and subsequent dose reduction was performed in 18 (36%) and 23 (46%) patients. There was one treatment-related death caused by septic infection.. Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil has a potential activity and is tolerable for heavily treated AGC with appropriate dose modification and patient selection.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Stomach Neoplasms; Treatment Outcome

Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC.. This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery.. Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms.. Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.

Topics: Adult; Aged; Antibodies, Bispecific; Antineoplastic Combined Chemotherapy Protocols; CD3 Complex; Docetaxel; Epithelial Cell Adhesion Molecule; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Peritoneal Neoplasms; Stomach Neoplasms

The aim of this study was to assess the feasibility of a modified FOLFOX regimen as first-line treatment in elderly patients with metastatic gastric cancer (GC) or colorectal cancer (CRC).. We included chemotherapy-naïve patients over 80 years old with metastatic GC or CRC in our study. From September 2008 to November 2014, 28 consecutive patients were enrolled and treated with modified FOLFOX.. The study population consisted of an equal number of GC and CRC patients. The median age was 82.2 years in the GC group and 81.1 years in the CRC group. The total number of administered cycles was 89 (with a median of 6 per patient) in the GC group and 112 (with a median of 8 per patient) in the CRC group. Median progression-free survival (PFS) and overall survival (OS) were 5.4 and 6.6 months in the GC group and 7.3 and 8.1 months in the CRC group, respectively. There was no significant difference in PFS (p = 0.941) and OS (p = 0.238) between the GC and the CRC group. The 1-year survival rates were 35.7% with GC and 42.9% with CRC. Common grade 3/4 hematology toxicities were neutropenia (10.7%) and anemia (14.3%). Salvage chemotherapy was administered to 1 patient with GC and 7 patients with CRC.. The modified FOLFOX regimen can be cautiously considered as a first-line treatment option in extremely elderly patients with metastatic GC or CRC.

Topics: Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Metastasis; Organoplatinum Compounds; Republic of Korea; Stomach Neoplasms; Survival Rate; Treatment Outcome

Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction.. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection.. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013.. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT.. The primary end point was overall survival.. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients.. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials.. clinicaltrials.gov identifier: NCT00849615.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Esophagogastric Junction; Fluorouracil; Gastrectomy; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Metastasectomy; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Young Adult

The identification of dynamic biomarkers in advanced gastric and oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to establish the optimal threshold and the clinical significance of CTC count in advanced GOA before and during treatment.. One hundred six patients with untreated advanced GOA were included in the ancillary study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the peripheral blood using the CellSearch system on day 0 (D0) and day 28 (D28). The prognostic value of CTCs at D0 and D28 was analysed by testing several thresholds.. At baseline, median CTC count was 1 (range, 0-415). While CTCs ≥1, 2 or 3 at D0 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS), CTCs ≥2 were the optimal threshold, on D0 or D28. CTCs ≥2 at D28 were also predictive of disease control. Taking into account both D0 and D28 CTC count defined 3 groups (low/low, high/low and low-high/high) with significantly different PFS (p = 0.0002) and OS (p = 0.003).. Quantification of CTCs at baseline and during treatment may be a useful prognostic tool in advanced GOA, as it is associated with worse PFS and OS. A threshold ≥2 CTCs seems to have the best discriminant value. Change in CTC count between baseline and D28 could help to tailor treatment to each individual patient.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cell Count; Disease Progression; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Neoplastic Cells, Circulating; Organoplatinum Compounds; Oxaliplatin; Prognosis; Stomach Neoplasms; Treatment Outcome

This phase I/II study was designed to determine the maximum tolerated dose of tivantinib in combination with standard dose FOLFOX for the treatment of patients with advanced solid tumors and to evaluate the safety and efficacy of this combination for patients with previously untreated metastatic adenocarcinoma of the distal esophagus, gastroesophageal (GE) junction, or stomach.. Patients with advanced solid tumors for which FOLFOX would be appropriate chemotherapy received escalating doses of tivantinib BID (days 1-14) in a standard 3 + 3 design in phase I. In phase II, patients with advanced GE cancer received standard FOLFOX day 1 and tivantinib (360 mg PO BID) days 1-14 of each 2-week cycle. Restaging occurred every four cycles. The primary phase II endpoint was response rate (RR).. Forty-nine patients were enrolled (15 on phase I and 34 on phase II). The expansion dose was established as tivantinib 360 mg BID in combination with FOLFOX. Thirty-two phase II patients were treated for a median of eight cycles (range, 1-38), with an overall RR of 38%. Treatment-related toxicities included neutropenia, fatigue, diarrhea, nausea, and peripheral neuropathy. Median progression-free survival (PFS) was 6.1 hmonths with a median time to progression of 7.0 months. Median overall survival was 9.6 months. Two patients remain on study at the time of this analysis.. The combination treatment of tivantinib plus FOLFOX in patients with advanced GE cancer showed a response and PFS in the range of historical controls for first-line FOLFOX therapy. However, two patients had extended time on study treatment (36 and 45 cycles) at the time of data cutoff.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Pyrrolidinones; Quinolines; Signal Transduction; Stomach Neoplasms; Time Factors; Treatment Outcome; United States

Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( P

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Epirubicin; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Risk Factors; Stomach Neoplasms; Survival Rate; Treatment Outcome; United States

The best choice of chemotherapy regimen for patients with metastatic gastric cancer is still debated. Although several studies support a superior efficacy of a triplet chemotherapy regimen over a doublet-based regimen, the magnitude of this benefit appears small and accompanied by an increased toxicity. Based on this background, we evaluated the outcome of patients with HER2-negative metastatic gastric cancer (mGC) who received in the clinical practice a triplet or doublet regimen as first-line therapy. A total of 165 patients (pts) with HER2-negative mGC treated outside of clinical trials at our department with FOLFOX-4 or ECX from 2012 and 2015 were included in our retrospective analysis: FOLFOX-4: 86 pts; ECX: 79 pts. Median progression-free survival (PFS) was 5.1 months for FOLFOX-4 and 5.6 months for ECX regimen, respectively. Median overall survival (OS) was 10.3 months for FOLFOX-4 and 10.9 months for ECX regimens.. grade 3-4 vomiting (12.6%), neutropenia (31.6%), mucositis (11.3%) and fatigue (22.7%) occurred more frequently in ECX regimen, while grade 3-4 peripheral neuropathy was more common with FOLFOX-4 (19.7%). Both evaluated regimens are active and safe in the palliation of HER2-negative mGC in the first-line setting: Three-drug chemotherapy regimen appear more active but offer only a slight improvement in OS with an increased G3-G4 toxicity. Our data suggest that a doublet therapy should be preferred in the clinical practice, preferentially reserving a three-drug combination to pts with bulky disease and/or to pts with initially unresectable locally advanced disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Receptor, ErbB-2; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

The median survival for patients with metastatic gastroesophageal adenocarcinoma is <12 months. Bevacizumab has demonstrated promising activity in metastatic gastroesophageal adenocarcinoma when used in combination with cisplatin-based regimens for patients from the Americas. We conducted a prospective phase II trial to investigate the efficacy of bevacizumab in combination with the oxaliplatin-based regimen, modified FOLFOX6, in patients with metastatic gastroesophageal adenocarcinoma.. Patients with untreated metastatic adenocarcinoma of the stomach, gastroesophageal junction, or distal esophagus received mFOLFOX6 (leucovorin 400 mg/m, fluorouracil 400 mg/m bolus and 2400 mg/m continuous infusion over 46 h, oxaliplatin 85 mg/m) and bevacizumab (10 mg/kg) every 2 weeks until disease progression or intolerance. Response by RECIST was evaluated by CT scan every 8 weeks. The primary objective was progression-free survival (PFS); secondary objectives were safety, response rate, and overall survival (OS).. A total of 39 patients with untreated metastastic gastroesophageal adenocarcinoma were enrolled between September 2008 and June 2012. Median number of cycles administered was 12 (range, 4 to 86). The confirmed response rate was 56.4% (3 complete response and 19 partial response). The median PFS was 7.8 months and median OS was 14.7 months. Three patients remain on treatment, and 11 patients are alive, of whom 6 have survived >24 months. Treatment-related grade 3/4 toxicities included neutropenia (33.3%), neuropathy (20.5%), thromboembolism (VTE) (7.7%), thrombocytopenia (7.7%), anemia (2.6%), hypertension (2.6%), and proteinuria (2.6%). We observed no GI perforations or grade 3/4 GI hemorrhagic events.. First-line mFOLFOX6 with bevacizumab for metastatic gastroesophageal adenocarcinoma was well tolerated and associated with longer PFS and OS compared with historical data from similar populations treated without bevacizumab. Our results suggest that the addition of bevacizumab to mFOLFOX6 may provide clinical benefit in American patients with metastatic gastroesophageal adenocarcinoma, a finding consistent with previous studies of first-line bevacizumab in combination with chemotherapy for this disease.

Topics: Adenocarcinoma; Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Drug Therapy, Combination; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prospective Studies; Stomach Neoplasms

The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.. A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.. Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. CLINICALTRIALS.. NCT02090153.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytochrome P-450 CYP2A6; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Pharmacogenomic Testing; Stomach Neoplasms; Tegafur

Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC.. To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC.. Randomized, double-blind, multicenter trial conducted from November 2012 to March 2014. Patients were 18 years or older with an adenocarcinoma of the stomach or gastroesophageal junction with metastatic disease not amenable for curative therapy. Tumor samples were centrally tested for MET expression using Ventana anti-Total c-MET (SP44) rabbit monoclonal antibody, HER2 status, and Lauren histologic subtype. MET-positive tumors were defined as at least 50% of tumor cells showing weak, moderate, and/or strong staining intensity (MET 1+/2+/3+, respectively) by immunohistochemistry.. Patients with HER2-negative, MET-positive GEC were enrolled and randomized 1:1 to receive mFOLFOX6 with or without onartuzumab (10 mg/kg).. Co-primary end points: overall survival in the intent-to-treat (ITT) population and in patients with MET 2+/3+ GEC. Secondary end points: progression-free survival (PFS), overall response rate (ORR), and safety.. Enrollment was stopped early due to sponsor decision, which was agreed with an independent data monitoring committee. At the data cutoff (April 25, 2014) there were 562 patients in the ITT population (n = 283 placebo plus mFOLFOX6 [median age, 58 y; 65% male]; n = 279 onartuzumab plus mFOLFOX6 [median age, 60 y; 67% male]); 109 (38.5%) and 105 (37.6%) of the ITT population were MET 2+/3+, respectively. Addition of onartuzumab to mFOLFOX6 did not significantly improve OS, PFS, or ORR vs placebo plus mFOLFOX6 in the ITT (OS hazard ratio [HR], 0.82; 95% CI, 0.59-1.15; P = .24; PFS HR, 0.90; 95% CI, 0.71-1.16; P = .43; ORR, 46.1% vs 40.6%) or MET 2+/3+ populations (OS HR, 0.64; 95% CI, 0.40-1.03; P = .06; PFS HR, 0.79; 95% CI, 0.54-1.15; P = .22; ORR, 53.8% vs 44.6%). Safety was as expected for onartuzumab.. Addition of onartuzumab to first-line mFOLFOX6 did not significantly improve clinical benefits in the ITT or MET 2+/3+ populations.. clinicaltrials.gov Identifier: NCT01662869.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Double-Blind Method; Epithelial-Mesenchymal Transition; Esophagogastric Junction; Female; Fluorouracil; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Proto-Oncogene Proteins c-met; Receptor, ErbB-2; Stomach Neoplasms

To evaluate the safety and efficacy of a concurrent three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) plus oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) regimen in completely resected gastric cancer patients with D2 lymph node dissection.. Patients with stage IB-IIIC gastric cancer (per the AJCC, 7th edition) who had undergone R0 and D2 gastrectomy were recruited. Two cycles of FOLFOX with concurrent 3D-CRT or IMRT (50.4 Gy/28f) were administered. One and an additional five cycles of FOLFOX were delivered before and after concurrent chemoradiotherapy, respectively. Primary endpoints were relapse-free survival (RFS) and overall survival (OS), with adverse events as secondary endpoints.. From 2008 to 2011, 110 patients were evaluable. The 1-, 2- and 3-year RFS and OS were 86.2, 72.2, 67.8 and 94.7, 87.2, 77.6%, respectively. On multivariate analysis, stage (≤ IIIA vs. >IIIA) was a statistically significant factor affecting both RFS and OS. Additionally, the T-category (≤ T4a vs. = T4b) was a statistically significant factor affecting only the RFS. The most commonly observed grade 3 or 4 adverse events were nausea and vomiting, decreased appetite, leukopenia/neutropenia and fatigue, each of which occurred in 14.5, 11.8, 9.1 and 6.4% patients, respectively.. Adjuvant 3D-CRT/IMRT to a dose of 50.4 Gy/28f with concurrent FOLFOX is safe and effective in patients following radical gastrectomy with D2 lymph node dissection.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Survival Rate; Treatment Outcome; Young Adult

This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine.. In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m(2)/day, days 1-5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m(2) followed by bolus 5-FU at 600 mg/m(2) with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m(2)) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival.. One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57-1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38-0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm.. As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Although leucovorin enhances the efficacy of fluorouracil, the anti-tumour activity of S-1 and leucovorin and their combination with oxaliplatin for patients with advanced gastric cancer is unknown. We compared the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy for advanced gastric cancer.. In this multicentre, randomised, open-label, phase 2 trial, we recruited chemotherapy-naive patients with unresectable or recurrent gastric cancer with measurable lesions aged 20 years or older from 25 general hospitals and specialist centres in Japan. Patients were randomly assigned (1:1:1) centrally to receive S-1 plus leucovorin (S-1 40-60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S-1 plus leucovorin and oxaliplatin (S-1 plus leucovorin and intravenous oxaliplatin 85 mg/m(2) on day 1, every 2 weeks), or S-1 plus cisplatin (S-1 40-60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m(2) on day 8, every 5 weeks). Randomisation was done with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors. The primary endpoint was independently reviewed overall response in the full analysis set. This trial is registered with Japic CTI, number 111635.. Between Oct 20, 2011, and Dec 17, 2012, we enrolled and randomly assigned 145 patients: 49 patients were assigned to S-1 plus leucovorin, 47 to S-1 plus leucovorin and oxaliplatin, and 49 to S-1 plus cisplatin. An objective response assessed by the independent review committee was achieved in 20 (43% [95% CI 28·3-57·8]) of the 47 patients in the S-1 plus leucovorin group, 31 (66% [50·7-79·1]) of the 47 patients in the S-1 plus leucovorin and oxaliplatin group, and 22 (46% [31·4-60·8]) of the 48 patients in the S-1 plus cisplatin group (Fisher's exact test, p=0·84 for S-1 plus leucovorin vs S-1 plus cisplatin, p=0·063 for S-1 plus leucovorin and oxaliplatin vs S-1 plus cisplatin, and p=0·038 for S-1 plus leucovorin and oxaliplatin vs S-1 plus leucovorin). The most common grade 3-4 adverse events were neutropenia (three [6%] of 48 patients in the S-1 plus leucovorin group vs 12 [26%] of 47 patients in the S-1 plus leucovorin and oxaliplatin group vs 17 [35%] of 49 patients in the S-1 plus cisplatin group), decreased appetite (six [13%] vs 14 [30%] vs 12 [24%]), anaemia (five [10%] vs seven [15%] vs 13 [27%]), and hyponatraemia (two [4%] vs two [4%] vs nine [18%]).. S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable toxic effects for patients with advanced gastric cancer. A phase 3 trial comparing S-1 plus leucovorin and oxaliplatin with S-1 plus cisplatin is underway.. Taiho Pharmaceutical.

Topics: Adenocarcinoma; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Feeding and Eating Disorders; Female; Humans; Hyponatremia; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Based upon preclinical data showing synergy with mTOR inhibition and platinum chemotherapy, this study explores the safety and tolerability of combining everolimus with mFOLFOX6 for patients with metastatic gastroesophageal adenocarcinoma.. Eligible patients with metastatic gastroesophageal adenocarcinoma received standard-dose mFOLFOX6 chemotherapy in combination with escalating doses of everolimus.. Six patients were accrued to the first dose level of 2.5 mg everolimus daily with mFOLFOX6. Overall, the toxicity profile was manageable with expected grade 3 toxicities of mucositis and neutropenia. The dose-limiting toxicity (DLT) included a week delay in therapy greater than 7 days as a result of the first 2 courses of mFOLFOX6. Two patients experienced DLTs at the first dose level due to delays in their treatment caused by prolonged grade 2 neutropenia and fever with fatigue. They were allowed to continue with a dose reduction of their chemotherapy. The median overall survival and progression-free survival were 20.3 and 14.5 months, respectively.. The combination of mFOLFOX6 and everolimus is an active regimen with 83% of the patients experiencing a partial response. p53 mutations were found in the 5 samples analyzed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Everolimus; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Stomach Neoplasms; Treatment Outcome

Adjuvant 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX6) are widely used for treating resected gastric cancer in clinics in China, but only few clinical trials have investigated its efficacy. Using propensity score matching, we evaluated the efficacy of adjuvant FOLFOX6 following D2 lymphadenectomy. Patients who received adjuvant FOLFOX6 following D2 lymphadenectomy (FOLFOX6, n = 113) or D2 lymphadenectomy only (surgery-only, n = 512) between 1998 and 2007 at our center were propensity score-matched; we identified a balanced 1:2 cohort, with 96 patients in the FOLFOX6 group and 192 patients in the surgery-only group. The overall survival (OS) was estimated using the Kaplan-Meier method; factors affecting survival were identified by Cox regression models. A nomogram incorporating independent prognosticators was constructed for predicting the 3-, 5-, and 7-year OS, and bootstrap validation was performed. The median follow-up was 9.3 years, and the 7-year OS was 52.1% in the FOLFOX6 group and 43.8% in the surgery-only group (P = 0.04), with an adjusted hazard ratio of 0.69 (95% confidence interval = 0.49-0.98). A prognostic nomogram was generated with the identified significant prognosticators (adjuvant FOLFOX6, number of total harvested nodes, the interaction effect between these two variables, tumor size, T and N stage). Internal validation of the nomogram revealed good predictive abilities, with a bootstrap-corrected concordance index of 0.70. Adjuvant FOLFOX6 following D2 lymphadenectomy is associated with survival benefit in resected gastric cancer. Receiving adjuvant FOLFOX6 can be developed into a nomogram with other independent prognosticators to refine OS prediction and estimation of benefit from adjuvant FOLFOX6 for resected gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; China; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Nomograms; Organoplatinum Compounds; Prognosis; Propensity Score; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Survival Rate; Time Factors

We evaluated the efficacy and safety of the modified FOLFOX6 (mFOLFOX6) regimen as a neoadjuvant chemotherapy in gastric cancer patients.. Seventy-three patients with T2-T4 or N+ were enroled. Preoperative chemotherapy consisted of three cycles of mFOLFOX6. The primary end points were the response rate and the R0 resection rate. Prognostic factors for overall survival (OS) were investigated using univariate and multivariate analyses.. Sixty-seven (91.8%) patients completed 3 cycles, with grade 3-4 toxicity arising in 33.0%. The radiology response rate was 45.8%. Sixty-seven (91.8%) patients receiving radical surgery showed different levels of histological regression of the primary tumour, with a ⩾50% regression rate of 49.2%. ypTNM stage (HR 4.045, 95% CI 1.429-11.446) and tumours of diffuse and mixed type (HR 9.963, 95% CI 1.937-51.235; HR 8.890, 95% CI 1.157-68.323, respectively) were significantly associated with OS. The pathologic regression rate (GHR; ⩾2/3/<2/3, ⩾50%/<50%) was statistically significantly associated with OS according to a univariate analysis.. Perioperative mFOLFOX6 was a tolerable and effective regimen for gastric cancer. The ypTNM stage was an independent predictor of survival. GHR ⩾50%/<50% could be used as a surrogate marker for selecting a postoperative chemotherapy regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Stomach Neoplasms

Docetaxel is active in esophagogastric junction (EGJ) adenocarcinoma, and DCF (docetaxel/cisplatin/5-fluorouracil) has shown good results in the neoadjuvant setting. Its high rate of grade 3-4 mucosal toxicity (stomatitis and diarrhea) has limited its widespread adoption. A more recent docetaxel-based triplet, FLOT (5-fluorouracil, oxaliplatin and docetaxel) may be better tolerated. We conducted a pilot study of FLOT chemotherapy in EGJ adenocarcinoma patients and dysphagia to prospectively assess the rate of grade 3-4 mucosal toxicity and of pathological complete response (pCR) rate. Dysphagia and quality of life were measured with validated questionnaires. Ten patients were enrolled. Grade 3-4 mucosal toxicity rate was 0 %; pCR rate was 11 %; and near-complete pathological response rate 11 %. Dysphagia improvement or resolution was seen in 90 % of patients, and quality of life was stable before and after chemotherapy. FLOT is a safe and active neoadjuvant chemotherapy option for EGJ adenocarcinoma and should be compared to other standard regimens in randomized trials.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Pilot Projects; Quality of Life; Stomach Neoplasms; Taxoids

The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined.. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles, followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and 0.60 in the MET-positive population. Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety.. Overall, 123 patients were enrolled (n = 62 onartuzumab, n = 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71-1.63; p = .71). In the MET-positive population, median PFS was 5.95 versus 6.80 months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60-3.20; p = .45). Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64-1.75; p = .83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45-2.78; p = .80). ORR was 60.5% for the onartuzumab group and 57.1% for placebo. Grade 3-5 adverse events (AEs) were seen in 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively.. The addition of onartuzumab to mFOLFOX6 in gastric cancer did not improve efficacy in an unselected population or in a MET immunohistochemistry-positive population.. The YO28252 study demonstrated that the addition of the anti-MET agent onartuzumab to mFOLFOX6 for treatment of gastric cancer did not improve efficacy in an overall study population or those selected for positive MET status by immunohistochemistry. This highlights the importance of correctly selecting biomarkers for targeted therapies. A multivariate analysis suggested that MET positivity may still be prognostic for worse median overall survival in gastric cancer; therefore, it is important to continue investigation into the optimal approach to inhibit MET signaling in gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Molecular Targeted Therapy; Organoplatinum Compounds; Proto-Oncogene Proteins c-met; Stomach Neoplasms

As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response.. This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively.. Overall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70-1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50-1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed.. Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted.. This study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland-Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Disease-Free Survival; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Fluorouracil; Humans; Indoles; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Pyrroles; Stomach Neoplasms; Sunitinib

We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ).. Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure-response analysis was undertaken.. Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69-1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure-response analysis indicated that patients with higher ramucirumab exposure had longer OS.. The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population.. NCT01246960.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Double-Blind Method; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Ramucirumab; Stomach Neoplasms; Treatment Outcome

The aim of this study was to evaluate the efficacy and safety of paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) as salvage chemotherapy in pretreated advanced gastric cancer. Fifty-two pretreated patients with the advanced gastric cancer were eligible for this study. The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of fluorouracil (2400 mg/m(2)) over a 46-hour period, every 14 days. From an intention-to-treat analysis, overall response rate and stable disease rate were 28.8 and 38.5%, respectively. The median time to progression and overall survival were 4.1 and 7.9 months, respectively. Grade 3 or 4 neutropaenia, thrombocytopaenia, fatigue, and neuropathy were 38.5, 15.4, 17.3, and 15.4%, respectively. The POF regimen is active in pretreated advanced gastric cancer as salvage chemotherapy, with a favourable toxicity profile.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Salvage Therapy; Stomach Neoplasms; Survival Analysis

Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery.. This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at least D2 lymph node resection. Median three cycles of fluorouracil chemotherapy were administered, and 45-Gy radiotherapy was delivered at 1.8 Gy/fraction concomitantly during the second cycle of chemotherapy. Local control, regional control, distant metastasis and overall survival rates were estimated.. The median age of the patients was 54 years (range 25-74 years). The most common grade III toxicities were nausea (10%) and neutropenia (9%). During radiotherapy, grade IV local skin reaction occurred in one patient. Median duration of follow-up was 47 months. Local, regional and distant recurrence developed in 9 (4%), 41 (18%) and 45 (20%) patients, respectively. Overall 5-year survival rate was 57.2%, and disease-free 5-year survival rate was 53.8%. Multivariate analysis identified less than 15 lymph node involvement as an independent predictor of better survival (p < 0.001).. Concomitant 5-FU-based chemoradiotherapy seems to be an effective and tolerable adjuvant regimen on local control and survival in curatively resected node-positive stomach cancer, particularly when combined with D2 resection.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate

In the context of gastric cancer, lymph node target volume delineation for post-operative radiotherapy is currently built on the traditional system of dividing the stomach and 2-D treatment methods. Here, we have proposed a new delineation approach with irradiation indications for lymph node stations. Its safety and efficacy were evaluated in a phase II clinical trial.. Fifty-four gastric cancer patients with D2 lymph node dissection received 2 cycles of FOLFOX4. They subsequently received concurrent chemoradiotherapy (45 Gy at 1.8 Gy per fraction, 5 fractions per week for 5 weeks) with a 5-fluorouracil/leucovorin regimen, followed by 4 additional FOLFOX4 cycles. The target volume included the remnant stomach, anastomosis site, tumor bed, and regional lymph nodes selected through our new approach by taking gastric arteries as references.. The most common grade 3-4 adverse event was neutropenia (14.8%). Neutropenia, anemia, and nausea were common grade 1-2 toxicities. No treatment-related deaths occurred during treatment. The 3-year overall, disease-free, and locoregional recurrence-free survival rates were 81.6%, 70.2%, and 91.1%, respectively. Eight patients developed peritoneal or distant metastases.. Using our new approach and irradiation indications, delineation of the target volume of post-operative lymph node stations was feasible and well tolerated after D2 resection in patients with gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymph Nodes; Male; Middle Aged; Organoplatinum Compounds; Stomach Neoplasms

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Disease-Free Survival; Epirubicin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Receptor, ErbB-2; Stomach Neoplasms

Treatment of patients with advanced or metastatic esophagogastric adenocarcinoma should not only prolong life but also provide relief of symptoms and improve quality of life (QOL). Esophagogastric adenocarcinoma mainly occurs in elderly patients, but they are underrepresented in most clinical trials and often do not receive effective combination chemotherapy, most probably for fear of intolerance. Using validated instruments, we prospectively assessed QOL within the randomized FLOT65+ phase II trial.. Within the FLOT65+ trial, a total of 143 patients aged ≥65 years were randomly allocated to receive biweekly oxaliplatin plus 5-fluorouracil (5-FU) continuous infusion and folinic acid (FLO) or the same regimen in combination with docetaxel 50 mg/m(2) (FLOT). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the gastric module STO22 were administered every 8 weeks until progression. Time to definitive deterioration of QOL parameters was analyzed and compared within the treatment arms.. The median age of patients was 70 years. Patients receiving FLOT exhibited higher response rates and had improved disease-free and progression-free survival (PFS). The proportions of patients with evaluable baseline EORTC QLQ-C30 and STO22 questionnaires were balanced (83 % in FLOT and 89 % in FLO). Considering evaluable patients with assessable questionnaires (n = 123), neither functioning nor symptom parameters differed significantly in favor of one of the two treatment groups. Particularly, there was no significant difference regarding time to definitive deterioration of global health status/quality of life from baseline (primary endpoint). Notably, patients receiving FLO or FLOT as palliative treatment (n = 98) achieved comparable QOL results.. Although toxicity was higher in patients receiving FLOT, no negative impact of the addition of docetaxel on QOL parameters could be demonstrated. Thus, elderly patients in need of intensified chemotherapy may receive FLOT without compromising patient-reported outcome parameters.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Quality of Life; Stomach Neoplasms; Taxoids; Treatment Outcome

For resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies.. Patients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m2/d by continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the preoperative study, or 45 Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence.. Between September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8-90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01-1.33] and 0.17 [0.03-0.89], p=0.04. Median overall survival time was 26.4 months in the preoperative study.. Feasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8-90.1) and 42.9% (CI 95%: 21.8-66%) in preoperative and postoperative settings respectively.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Dose Fractionation, Radiation; Feasibility Studies; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Multivariate Analysis; Postoperative Period; Preoperative Period; Stomach; Stomach Neoplasms; Survival Analysis; Treatment Outcome

With a median overall survival of only 9-13 months in patients with advanced gastric cancer (GC), the quality of life (QoL) during the palliative treatment remains a key issue. Furthermore, when combinations of two or three drugs are used, the impact on QoL should be carefully evaluated. This was studied within the GATAC trial in patients sequentially treated with docetaxel and irinotecan with 5-fluorouracil and leucovorin (5-Fu/Lv). Patients with previously untreated advanced GC were randomly assigned to start with docetaxel 45 mg/m(2) (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus and 44 h infusion of 5-Fu/Lv (D1, q2 weeks). After four courses, there was a prescheduled crossover to the alternative regimen for four additional courses. QoL was measured with the EORTC QLQ-C30 questionnaire at the start of the treatment, at crossover and after completing treatment with both regimens. Eighty-one patients were randomized, and 78 patients started treatment. A total of 191 completed QoL questionnaires were collected. There were no statistically significant differences in QoL scores between the two treatment groups and no changes in mean scores during the 16 weeks of treatment. During the last 8 weeks of treatment, a significantly larger portion of patients with radiological response reported sustained or better QoL scores than those with no radiological response (82 vs. 50%, p = 0.007). Chemotherapy in advanced GC did not affect QoL average scores. Patients with non-responding tumours reported more often a decline in the global QoL score. The concept of the pre-scheduled switch of chemotherapy regimens prior to progression should be further studied in this disease, as it appears effective, tolerable and not to negatively affect QoL.

Topics: Adult; Aged; Antineoplastic Agents; Camptothecin; Docetaxel; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Quality of Life; Stomach Neoplasms; Surveys and Questionnaires; Taxoids; Treatment Outcome

Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer.. Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm).. From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively.. A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy.. ClinicalTrials.gov Identifier: NCT01640782.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Docetaxel; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Taxoids

Gastric cancers may harbor a subset of cells with cancer stem cell (CSC) properties, including chemotherapy resistance, and CD44 is a gastric CSC marker. The Hedgehog (HH) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis. Here, we examine the role of HH signaling in CD44(+) gastric cancer cells.. Gastric cancer cell lines, tumor xenografts, and patient tumors were examined.. Gastric cancer cell lines AGS, MKN-45, and NCI-N87 grown as spheroids or sorted for CD44(+) were found to have upregulation of HH pathway proteins. HH inhibition using Smoothened (Smo) shRNA or vismodegib (VIS) decreased spheroid formation and colony formation. CD44(+) cells, compared with unselected cells, were also resistant to 5-fluorouracil and cisplatin chemotherapy, and this resistance was reversed in vitro and in xenografts with Smo shRNA or VIS. CD44(+) cells also had significantly more migration, invasion, and anchorage-independent growth, and these properties could all be blocked with HH inhibition. Clinical tumor samples from a phase II trial of chemotherapy with or without VIS for advanced gastric cancer were analyzed for CD44 expression. In the chemotherapy alone group, high CD44 expression was associated with decreased survival, whereas in the chemotherapy plus VIS group, high CD44 expression was associated with improved survival.. HH signaling maintains CSC phenotypes and malignant transformation phenotypes in CD44(+) gastric cancer cells, and HH inhibition can reverse chemotherapy resistance in CD44(+) cells. Gastric cancer is a heterogeneous disease, and the strategy of combining chemotherapy with HH inhibition may only be effective in tumors with high CD44 levels.

Topics: Adenocarcinoma; Anilides; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Cell Movement; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Female; Flow Cytometry; Fluorescent Antibody Technique; Fluorouracil; Hedgehog Proteins; Humans; Hyaluronan Receptors; Leucovorin; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Prognosis; Pyridines; Receptors, G-Protein-Coupled; RNA, Small Interfering; Signal Transduction; Smoothened Receptor; Spheroids, Cellular; Stomach Neoplasms; Survival Rate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Combination of fluoropyrimidines and a platinum derivative are currently standards for systemic chemotherapy in advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Nevertheless, individual likelihood for response to these therapeutic regimes remains uncertain. Even more, no predictive markers are available to determine which patients may benefit more from oxaliplatin versus cisplatin or vice versa. The new invasion and stem cell markers VEGFR-3 and CXCR4 have been linked prognostically with more aggressive esophagogastric cancer types. Thus, we aimed to assess correlations of VEGFR-3 and CXCR4 expression levels with clinical outcome in a randomized phase III study of patients with oxaliplatin/leucovorin/5-FU (FLO) versus cisplatin/leucovorin/5-FU (FLP).. The patients data examined in this study (n = 72) were from the collective of the FLO vs. FLP phase III AIO trial. Tumour tissues were stained via immunohistochemistry for VEGFR-3 and CXCR4 expression and results were evaluated by two independent, blinded investigators.Outcome parameter: Survival analysis was calculated for patients receiving FLO vs. FLP in relation to VEGFR-3 and CXCR4 expression.. 54% and 36% of the examined tumour tissues showed strong positive expression of VEGFR-3 and CXCR4 respectively. No superiority of each regime was detected in terms of overall survival (OS) in the whole population. Patients with strong expression of CXCR4 on their tumour tissues profited more in terms of OS under the treatment of FLP (mOS: 28 vs 15 months, p = 0.05 respectively). Patients with negative VEGFR-3 and CXCR4 expression had a trend to live longer when FLO regime was applied (mOS: 22 vs. 9 months, p = 0.099 and 20 vs. 10 months, p = 0.073 respectively). In an exploratory analysis of patients older than 60 years at diagnosis, we observed a significant benefit in overall survival for VEGFR-3 and CXCR4-positive patients when treated with FLP (p = 0.002, p = 0.021 respectively).. CXCR4 positive patients profited in terms of OS from FLP, whereas FLO proved to be more effective in CXCR4 and VEGFR-3 negative patients. Our results suggest, despite the limited size of the study, a predictive value of these biomarkers concerning chemotherapy with FLP or FLO in advanced esophagogastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophagogastric Junction; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Receptors, CXCR4; Stomach Neoplasms; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-3

This phase II trial investigates the efficacy and safety of low-dose everolimus in combination with cisplatin-fluorouracil chemotherapy in patients with advanced gastric cancer.. Eligible patients with chemotherapy-naïve advanced gastric cancer received low-dose everolimus (10 mg p.o. on days 1, 8 and 15) plus cisplatin and a weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL) chemotherapy (cisplatin 35 mg/m(2) intravenous infusion for 24 h on days 1 and 8, 5-fluorouracil 2,000 mg/m(2) and leucovorin 300 mg/m(2) intravenous infusion for 24 h on days 1, 8 and 15) every 28 days. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.0.. Forty patients (19 men; 21 women; median age, 54.1 years; range, 33.7-73.3 years) received a median of 6 (range, 1-30; 95% CI, 4.9-8.0) cycles of study treatment. The ORR was 52.5% (21 confirmed partial response). The median progression-free survival and overall survival were 6.9 (95% CI, 4.9-8.4) and 10.5 (95% CI, 8.6-12.3) months, respectively. Most adverse events were mild.. Adding low-dose everolimus to cisplatin-HDFL chemotherapy failed to increase the ORR as in a preplanned statistical assumption but may prolong progression-free survival in treatment-naïve advanced gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Everolimus; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Pilot Projects; Sirolimus; Stomach Neoplasms; Taiwan; Treatment Outcome

A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis.. Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm).. Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0). Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm. Four patients in the GYMS arm survived >12 months, 2 patients close to 2 years at last follow-up, and 1 patient more than 4 years, with 2 of these patients still alive. No patient in the SA arm lived beyond 11 months. All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index (PCI) of ≤ 15.. Maximal cytoreductive surgery combined with regional (HIPEC) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Cancer, Regional Perfusion; Female; Fluorouracil; Gastrectomy; Humans; Hyperthermia, Induced; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Peritoneum; Prospective Studies; Stomach Neoplasms

Neoadjuvant chemotherapy has been shown to improve the rate of complete (R0) resection and downstaging in patients with localized gastric cancer. There are few reports, however, regarding its impact on postoperative morbidity and mortality. The aims of this study were to analyse complication and mortality rates after neoadjuvant chemotherapy using a modified regimen of folinic acid, 5-fluorouracil and oxaliplatin (mFOLFOX6) for locally advanced gastric cancer (AGC), compared with rates in patients who underwent surgery without neoadjuvant chemotherapy.. Data were collected from patients with AGC enrolled in a phase II trial of four cycles of neoadjuvant mFOLFOX6 followed by surgery, between January 2005 and June 2008 at two of three institutions, and compared with those from a cohort of patients with AGC who underwent surgery alone at one of the institutions in 2006.. Among 51 patients who received neoadjuvant chemotherapy, there were no deaths and a morbidity rate of 24 per cent after surgery. Comparison of 48 patients in one institution who received neoadjuvant chemotherapy with 92 patients who had surgery alone in the same institution showed no increase in postoperative morbidity (23 versus 29 per cent; P = 0·417). Combined resection was the only risk factor for postoperative morbidity after neoadjuvant chemotherapy.. Neoadjuvant chemotherapy with mFOLFOX is a safe treatment for patients with localized AGC, and does not increase postoperative morbidity or mortality.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Postoperative Complications; Stomach Neoplasms

Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.. In this phase II study (NCT00515216 registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/NCT00515216), patients with "good risk" TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%).. The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response.. In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers.. ClinicalTrials.gov NCT00515216.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cardia; Enhancer Elements, Genetic; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Gene Frequency; Genetic Variation; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Prospective Studies; Risk; Stomach Neoplasms; Thymidylate Synthase; Treatment Outcome

To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma.. This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life.. In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events [AEs], 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81).. FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Cisplatin; Deoxycytidine; Epirubicin; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; France; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Prospective Studies; Quality of Life; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymphocyte Count; Male; Middle Aged; Neoadjuvant Therapy; Neutrophils; Organoplatinum Compounds; Predictive Value of Tests; Prognosis; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals.. Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0.. A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival.. Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Carcinoma, Signet Ring Cell; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies; Stomach Neoplasms; Survival Rate; Time Factors; Young Adult

To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer.. Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles.. The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P>0·05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade 3/4 neutropenia, with an incidence of 43·7% in the TS arm and 16·3% in the TLF arm, respectively (P<0·05). Other severe adverse events were infrequent and not significantly different between the groups.. The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Young Adult

The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy.. Patients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR.. One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009).. A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Survival; Survival Rate; Taxoids; Vitamin B Complex

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Digestive System Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Stomach Neoplasms

To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas.. Patients were treated in two matuzumab dose groups with the first cohort of patients receiving 400 mg matuzumab in combination with PLF. Based on the safety observations the next cohort of patients received 800 mg matuzumab. The study was conducted in two parts, with phase A, designed to assess the safety and tolerability of the combination, and phase B designed to be a treatment continuation for those patients benefiting from treatment. Treatment cycles were 7 weeks each. Each patient received the dose of matuzumab they were assigned to at study entry for the duration of the study.. Fifteen EGFR-positive patients were enrolled into the two matuzumab dose groups; 400 mg dose n=7; 800 mg dose n=8. All patients experienced at least one adverse event (AE). No patient experienced any serious AE which was considered to be related to matuzumab. Two grade 3 AEs possibly related to matuzumab occurred in 2 different patients (13.3 %), both in the 800 mg dose group. No dose-limiting toxicity (DLT) was observed in the 400 mg group. The maximum tolerated dose of matuzumab was not reached. The best confirmed overall response rate was 26.7 %.. Matuzumab, in combination with PLF, demonstrated an acceptable safety profile with modest anti-tumor activity.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; ErbB Receptors; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Skin; Stomach Neoplasms

Elderly patients are generally underrepresented in the study populations of combination chemotherapy trials. This study evaluates the efficacy and safety of a modified FOLFOX regimen in elderly patients with metastatic gastric cancer and presenting associated disease(s).. A total of 43 patients aged ≥70 years received oxaliplatin 85 mg/m(2) together with 6S-leucovorin 200 mg/m(2) on day 1, followed by a 46-h infusion of 5-fluorouracil 2,400 mg/m(2), every 2 weeks. Assessment of response was performed every four cycles according to RECIST criteria.. Median patient age was 74 years (range, 70-83 years). Overall response rate was 34.9% [95% confidence interval (CI), 20.6-49.1, with 3 complete responses and 12 partial responses. Grade 3 neutropenia occurred in 4 patients (9.3%), fatigue in 3 patients (7.0%), and vomiting in 2 patients (4.6%). Grade 2 and 3 peripheral neuropathy was observed in 5 patients (11.6%) and 1 patient (2.3%), respectively. No treatment-related death was observed. Median progression-free and overall survival were 6.8 and 10.5 months, respectively.. This modified FOLFOX regimen is an active and well-tolerated treatment for elderly patients with metastatic gastric cancer and also represents a good therapeutic option in patients with associated disease(s).

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Metastasis; Organoplatinum Compounds; Stomach Neoplasms; Survival Rate; Treatment Outcome

The aim of this study was to evaluate the efficacy of irinotecan (CPT-11) monotherapy and CPT-11 plus 5-fluorouracil (5-FU)/leucovorin (LV) combination (mFOLFIRI) as second-line treatment in patients with advanced gastric cancer (AGC).. A total of 59 patients were randomly assigned to either CPT-11 (150 mg/m(2) iv on day 1) or mFOLFIRI (CPT-11 150 mg/m(2) plus LV 20 mg/m(2) on day 1 followed by 5-FU 2,000 mg/m(2) over 48 h), every 2 weeks. The primary end point was objective response rate (ORR).. Following random assignment, 29 patients received CPT-11 and 30 patients mFOLFIRI. The ORR was 17.2 % [95 % confidence interval (CI) 3.4-30.9] and 20.0 % (95 % CI 5.6-34.3) for the CPT-11 and mFOLFIRI arms, respectively (P = 0.525). There was no significant difference in median progression-free survival: 2.2 months (95 % CI 0.2-4.3) for CPT-11 versus 3.0 months (95 % CI 2.0-3.7) for mFOLFIRI (P = 0.481) or in median overall survival: 5.8 months (95 % CI 3.0-8.7), compared with 6.7 months (95 % CI 5.3-8.2) (P = 0.514). Grade 3/4 toxicity was observed in 21 and 28 events in the CPT-11 and mFOLFIRI arms, respectively.. Although this study had a small sample size and limited statistical power, CPT-11 monotherapy and mFOLFIRI appear to be equally active and tolerable as second-line chemotherapy for AGC. The addition of 5-FU/LV to CPT-11 did not significantly improve efficacy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Combination therapy with docetaxel, cisplatin, and 5-FU has been shown to increase time to progression (TTP) and overall survival (OS) for patients with advanced gastric cancer; this regimen is limited by significant toxicity, including complicated neutropenia. This study was designed to incorporate docetaxel into a tolerable biweekly (once every 2 weeks) oxaliplatin-based chemotherapy regimen. Patients with measurable advanced and metastatic gastric or gastroesophageal cancer, aged >18 years, and with ECOG two or less, received oxaliplatin 85 mg/m(2), docetaxel 50 mg/m(2) on day 1, leucovorin 200 mg/m(2) on days 1 and 2, and 5-FU 1,200 mg/m(2) 24-h infusion on days 1 and 2 of every 2-week cycle. Toxic effects were graded according to NCI-CTC version 3. Responses were classified according to World Health Organization criteria. Fifty patients were included, 47 assessed for efficacy and toxicity. Median age was 55 years. The majority had metastatic disease (72 %). The over all response was observed in 55.3 % patients. Median TTP and OS were 6 and 10 months, respectively. Grade 3 or 4 hematological toxic effects were included neutropenia, leukopenia, and thrombocytopenia observed in 21 (44.7 %), 12 (25.5 %), and 1 (2.1 %) patients, respectively. Non-hematological were diarrhea (14.9 %), fatigue (12.7 %), and peripheral neuropathy (8.5 %). Complicated neutropenia (febrile neutropenia associated with infection) was observed in one (2.1 %) patient only. Biweekly FLOT regimen has tolerable toxicity, and efficacy in line with that of DCF protocol. The FLOT regimen needs more evaluation to be considered as alternative to DCF.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Esophageal Neoplasms; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Taxoids; Treatment Outcome; Young Adult

The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients.. Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks.. Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%).. Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Perioperative Care; Prognosis; Prospective Studies; Quality of Life; Stomach Neoplasms; Survival Rate; Taxoids

A chemotherapy regimen with oxaliplatin, fluorouracil, and leucovorin is commonly used to treat advanced gastric cancer (AGC). This study was designed to compare the efficacy and the safety of oxaliplatin plus fluorouracil/leucovorin administered biweekly (mFOLFOX6) between elderly patients aged over 65 years and younger counterparts with AGC.. This analysis included 82 AGC patients (≥65:31, <65:51). Patients with previously untreated chemo-naïve advanced adenocarcinoma of the stomach received oxaliplatin 85 mg/m(2), 5-FU bolus 400 mg/m(2) on day 1 and 5-FU 1,500 mg/m(2), leucovorin 75 mg/m(2) 22 h infusion on days 1 and 2 every 2 weeks. The aim of the study was to compare efficacy and safety, including response rate (RR), progression-free survival (PFS), overall survival, and grade ≥3 adverse events, between patients aged ≥65 years and patients aged <65 years.. Median progression-free survival (PFS) was not significantly different between both groups (≥65: 5.8 months, <65: 5.7 months, respectively, HR 0.77, 95% CI: 0.44-1.16, P = 0.18). Median overall survival was not significantly different between both groups (≥65: 10.3 months, <65: 9.5 months HR 0.83, 95% CI: 0.50-1.37, P = 0.46). The rate of grade 3 or 4 neutropenia did not differ with age group (≥65: 51.6%, <65: 43.1%); nor did the rates of neutropenic fever (≥65: 16.1%, <65: 5.9%), and infection without neutropenia (≥65: 3.2%, <65: 3.9%). Rates of grade ≥3 toxicities such as thrombocytopenia, nausea/vomiting, or peripheral neuropathy were not significantly different between the two groups.. mFOLFOX6 maintains its efficacy and safety in elderly patients aged over 65 years in comparison with AGC patients aged <65 years. Its judicious use should be considered regardless of age.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.. Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50 mg/m(2) as a 30-min infusion on day 1, leucovorin 200 mg/m(2) in a 2-h infusion, and 5-FU 2,800 mg/m(2) in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75 mg/m(2), every 3 weeks).. Thirty-four patients were enrolled, with an average age of 64 years (range 34-69). The main cumulative grade 3-4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9-54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6 months, respectively.. For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Taxoids; Treatment Outcome

To evaluate the value of normalization window of tumor vasculature (NWTV) in patients with unresectable gastric cancer undergoing neoadjuvant chemotherapy.. From October 2010 to March 2011, 93 patients with unresectable advanced or locally advanced gastric carcinoma were prospectively collected and randomly divided to Group A(n=30), Group B(n=29), and Group C(n=34). Group A received FOLFOX4 as conventional neoadjuvant chemotherapy. Group B received FOLFOX4 plus bevacizumab. The treatment was adjusted in Group C according to the hypothesis of NWTV with neoadjuvant chemotherapy delivered 5 days after bevacizumab treatment. The efficacy, drug toxicity and clinical outcome were assessed and compared between the three groups.. There were no significant differences among the 3 groups in demographics(P>0.05). All the patients completed the neoadjuvant chemotherapy. Efficacy and toxicity between the three groups were comparable(P>0.05). The rates of tumor downstaging in the three groups were 56.7%(17/30), 72.4%(21/29), 85.3%(29/34), respectively, with a significantly lower downstaging rate in Group C as compared to Group A(P<0.05). R0 resection rates were 23.3%(7/30), 27.6%(8/29), 52.9% (18/34), respectively, with significantly higher R0 resection rate in Group C as compared to Group A and Group B(All P<0.05). There was no perioperative death in this cohort. Postoperative complications were comparable among the 3 groups(P>0.05).. Anti-angiogenesis agent can improve the efficacy of neoadjuvant chemotherapy in unresectable gastric cancer. Furthermore, administration according to NWTV may achieve better outcomes.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neovascularization, Pathologic; Organoplatinum Compounds; Prospective Studies; Stomach Neoplasms; Treatment Outcome; Young Adult

Pre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced gastric cancer.. A total of 56 histologically proven gastric cancer patients, who were considered to be stage II or higher with metastatic lymph nodes and with or without distant metastasis (T2-4, N1-3, and M0-1), were treated with a neoadjuvant chemotherapy. Patients received a combination of intravenous 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) on days 1-5, and intra-arterial etoposide (80 mg/m2) and cisplatin (80 mg/m2) on days 6 and 20. After two cycles of preoperative chemotherapy, patients with resectable tumors underwent laparotomy.. All patients finished two cycles of chemotherapy. The overall response rate was 78.57% (44 cases), of which 7.14% (four cases) clinical complete response. Forty-six patients underwent resection, including 21 initially unresectable diseases. R0 resection rate for prechemotherapy resectable and unresectable diseases was 96.15% (25/26 cases) and 66.67% (20/30 cases), respectively. Pathological complete response was observed in 8.70% of patients. Toxicity was moderate and there were no chemotherapy-related deaths. With a median follow-up of 31 months (range 6-76 months), the 5-year survival rate for the whole group and patients with initially resectable tumors were 21.8% and 42.3%, respectively. The median survival for initially resectable and unresectable patients were 41 months (95%CI, 31.006-50.994) and 18 months (95%CI, 13.399-22.601; P<0.01), respectively.. Preliminary results proved that the combined intensive chemotherapy was a safe and promising regimen for pre-operative treatment of advanced gastric cancer.

Topics: Adult; Aged; Cisplatin; Etoposide; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Retrospective Studies; Stomach Neoplasms

Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses.. In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy.. Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect.. Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy in such patients.. In the first phase of the study, we investigated the maximum tolerated dose and recommended dose in Cycle 1 of fluorouracil, l-leucovorin and paclitaxel, at two dose levels [Level 1 (n = 6): 5-fluorouracil/l-leucovorin/paclitaxel = 500/250/60 mg/m(2); Level 2 (n = 6): 600/250/80 mg/m(2) on Days 1, 8 and 15, every 28 days]. Nineteen additional patients at the recommended dose level were enrolled in the second phase to investigate the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy. The primary endpoint in the second phase was the completion rate of two cycles.. Dose-limiting toxicities were observed in a patient at Level 1 with Grade 4 gastrointestinal perforation (the site of primary tumor), and in two patients at Level 2 with Grade 3 febrile neutropenia and Grade 3 infection, respectively. In Cycle 2, treatment-related death occurred at Level 2 in one patient who had Grade 4 febrile neutropenia with pneumonia. The maximum tolerated dose was set at Level 2, and the recommended dose was determined as Level 1. In the second phase, the completion rate of two cycles was 92% and the ascites response was 44%. Median progression-free survival was 4.2 months and overall survival was 8.0 months. Grade 3/4 neutropenia was observed in 12% of patients.. Fluorouracil, l-leucovorin and paclitaxel at Level 1 is feasible as first-line treatment for peritoneal disseminated gastric cancer patients with massive ascites or inadequate oral intake.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Disease-Free Survival; Drug Administration Schedule; Eating; Feasibility Studies; Female; Fluorouracil; Humans; Intestinal Perforation; Kaplan-Meier Estimate; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms

To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.. The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed.. Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively).. Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Chemoradiotherapy; Disease-Free Survival; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Period; Radiotherapy Dosage; Stomach Neoplasms

Tumor vascular endothelial growth factor (VEGF) is a key angiogenic factor and may have an impact on tumor progression and response to chemotherapy. The insulin-like growth factor (IGF) system is related to cell proliferation and tumor growth. However, there is limited available data regarding the clinical and prognostic significance of VEGF or IGF-1 in advanced gastric cancer. The aim of this study was to evaluate the prognostic significance of serum VEGF and IGF-1 levels in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX).. The study population consisted of 100 advanced gastric cancer patients (median age 56 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by a 5-fluorouracil (5-FU) bolus 400 mg/m(2) and 22 h of continuous infusion of 600 mg/m(2) on days 1-2. Treatment was repeated in 2-week intervals. The levels of serum VEGF and IGF-1 were measured using enzyme-linked immunoassays.. There was a significant correlation between the serum level of VEGF and Lauren's classification (p = 0.030) and previous operations (p = 0.010). IGF-1 was associated with the number of metastases (p = 0.012). The median level of serum VEGF was decreased after FOLFOX chemotherapy (p = 0.034). However, none of the measured serum markers were significantly correlated with response. In univariate analysis, overall survival (p < 0.001) was significantly shorter in patients with high serum levels of VEGF. Multivariate analysis revealed that VEGF was an independent factor for overall survival (HR 2.221; 95% CI 1.377-3.583, p = 0.001). Furthermore, IGF-1 had no significant influence on the clinical outcome.. A high level of serum VEGF is an independent prognostic factor in patients with advanced gastric cancer treated with chemotherapy. This may help to identify the patients who are more sensitive to the FOLFOX regimen.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Fluorouracil; Humans; Insulin-Like Growth Factor I; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Organoplatinum Compounds; Prognosis; Stomach Neoplasms; Survival Rate; Treatment Outcome; Vascular Endothelial Growth Factor A

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer.. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included.. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively.. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Polyethylene Glycols; Recombinant Proteins; Stomach Neoplasms; Taxoids; Treatment Outcome

To evaluate the effect of 2 regimens of postoperative combination chemotherapies on the prognosis of early stage gastric cancer patients.. A total of 268 patients with stage II gastric cancer underwent D2 resection in our Cancer Center between January 1990 and December 2006 were recruited. Among them, 34 patients received the FAM regimen (5-fluorouracil [5-FU] 600 mg/m(2) intravenous [IV] drip on days 1, 8, 29, and 36; doxorubicin 30 mg/m(2) IV bolus injection on days 1 and 29; and mitomycin-C 10 mg/m(2) IV bolus injection on day 1; repeated every 8 weeks) and 81 patients received the FOLFOX regimen (oxaliplatin 100 mg/m(2) IV drip on days 1 and 15; leucovorin 400 mg/m(2) IV drip on days 1 and 15; 5-FU 400 mg/m(2) IV bolus injection; 5-FU 2.4/3.0 mg/m(2) continuous IV infusion for 48 hours on day 1, 2, 15, and 16; repeated every 4 weeks for at least 4 cycles). Patients were followed-up until December 2008. The Kaplan-Meier method was used to compare survival rates between treatment groups.. The 1-, 3-, 5-, and 10-year survival rates for the patients who received postoperative chemotherapy versus the patients who underwent surgery only were 98%, 84%, 58%, 18% versus 96%, 78%, 59%, 22%, respectively (P > 0.05). Furthermore, the survival rates for patients who received the FAM and FOLFOX regimens were not significantly different (P > 0.05).. Postoperative adjuvant chemotherapy did not produce survival benefits for the patients with stage II gastric cancer. Randomized controlled clinical trials are demanded to confirm the finding from this study.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Infusions, Intravenous; Injections, Intravenous; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Staging; Organoplatinum Compounds; Patient Selection; Postoperative Period; Stomach Neoplasms; Treatment Failure

Both docetaxel-based and irinotecan-based chemotherapy has been demonstrated as active combination regimen in either first-line or second-line setting for metastatic gastric cancer. The purpose of this trial was to evaluate the two active regimens, docetaxel/cisplatin and FOLFIRI, as first- and second-line chemotherapy and to compare the sequence of the two regimens in terms of efficacy and tolerability.. Eligible patients were randomized to receive one of the two treatment arms: Arm A-DP (docetaxel 75 mg/m(2) D1, cisplatin 75 mg/m(2) D1 repeated every 3 weeks) until progression or unacceptable toxicity as the first-line treatment which was followed by FOLFIRI (irinotecan 150 mg/m(2) D1, leucovorin 100 mg/m(2) D1, 5-fluorouracil 3,000 mg/m(2) D1-2 for 48 h every 2 weeks) upon disease progression as second-line chemotherapy; Arm B-FOLFIRI as the first-line treatment until disease progression or unacceptable toxicity then followed by DP as the second-line treatment upon documented disease progression.. Between April 2005 and Aug 2008, 58 patients were enrolled (Arm A, n = 28; Arm B, n = 30). Median follow-up was 38.2 months. The overall response rate (ORR) of the first-line chemotherapy was 25.0% with DP (Arm A1) and 13.3 with FOLFIRI (Arm B1) (P = 0.322). The tumor control rate (TCR) of first-line chemotherapy was 82.1% with DP and 66.7% with FOLFIRI (P = 0.209). The median first progression-free survival (1st PFS) was 4.3 months with DP and 3.4 months with FOLFIRI (P = 0.547). The overall response rate of second-line chemotherapy was 20.0% with FOLFIRI (Arm A2) and 27.2% with DP (Arm B2) (P = 0.296). The tumor control rate of second-line chemotherapy was 46.7% with FOLFIRI and 50.0% with DP. The median second progression-free survival (2nd PFS) was 8.1 months with Arm A and 6.7 months with Arm B (P = 0.865). The median overall survival was 12.5 months (95% CI 8.17-16.83) in Arm A and 13.4 months (95% CI 9.99-16.81) in Arm B (P = 0.674). In safety profile, the incidence of neutropenic fever was comparable among the 4 arms ranging from 0 to 3.9%.. The ORR, TCR of Arm A (DP → FOLFIRI) were not different from those of Arm B (FOLFIRI → DP). There was no statistically significant difference in 1st PFS, 2nd PFS, and OS of both arms. Although the trial was terminated early due to poor patient accrual, we found that both DP and FOLFIRI regimens were tolerable with comparable efficacies regardless of the sequence administered.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Chemoradiotherapy; Dose-Response Relationship, Drug; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms

Cetuximab plus irinotecan/folinic acid/5-fluorouracil (5-FU) (IF) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors. Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out.. Patients received weekly cetuximab (400 mg/m(2) on day 1, subsequently 250 mg/m(2)) plus irinotecan (80 mg/m(2)) and a 24-hour continuous infusion of folinic acid (200 mg/m(2)) and 5-FU (1500 mg/m(2)) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until progressive disease (PD).. The most common grade 3/4 toxic effects in 49 patients were diarrhea (15%) and skin toxic effects (14%). In 48 assessable patients, the overall response rate was 46% and disease control rate was 79%. Median progression-free survival (PFS) and overall survival (OS) was 9.0 months [95% confidence interval (CI) 7.1-15.6] and 16.5 months (95% CI 11.7-30.1), respectively. Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors (P = 0.041). Tumor PTEN expression was associated with longer PFS (P = 0.035) and OS (P = 0.0127) than no PTEN expression.. Cetuximab plus IF was well tolerated and efficacy data were encouraging. This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXPAND trial.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Treatment Outcome

To investigate the efficacy and toxicity of FOLFOX4 regimen and LV5Fu2 regimen in patients with advanced gastric adenocarcinoma after curative gastrectomy.. Eighty patients with gastric adenocarcinoma after curative gastrectomy were randomized to receive a 2-h infusion of leucovorin (LV; 200mg/m(2)/d) followed by a 5-fluorouracil (5-FU) bolus (400mg/m(2)/d) and 22-h infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1 (FOLFOX4 regimen or LV5Fu2 regimen). The observation points were recurrence free survival, overall survival and toxicity of the two groups.. All patients had received curative gastrectomy (R0 resection) before received either of the two regimens. The 3-year recurrence free survival rate and the 3-year overall survival rate in FOLFOX4 group were all significantly better than those in the control group (median, 30.0 months vs. 16.0 months, P<0.05; 36.0 months vs. 28.0 months, P<0.05). COX multivariant analysis was used to evaluate the prognostic factors and oxaliplatin was found to be the independent prognostic factor and could improve the survival rate in FOLFOX4 group. Grade 3/4 peripheral neuropathy occurred in 19% in FOLFOX4 group. There was no significant difference between the two groups in neutropenia, leukopenia, anemia, gastrointestinal reaction and so on. Three patients in each group were lost to follow up during treatment.. FOLFOX4 regimen showed good efficacy and an acceptable safety profile for patients with advanced gastric adenocarcinoma after curative gastrectomy compared with the control group. It may prove to be a suitable alterative regimen in this indication.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Patient Selection; Prospective Studies; Severity of Illness Index; Stomach Neoplasms; Treatment Outcome

This study was conducted to evaluate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil (5-FU) and leucovorin as first-line treatment for patients with advanced gastric cancer.. Eligible patients with histologically confirmed advanced or metastatic gastric cancer were enrolled. The chemotherapeutic regimen consisted of paclitaxel (100 mg/m(2) on day 1) as a 3-hour intravenous infusion, followed sequentially by leucovorin (400 mg/m(2) on day 1) as a 2-hour intravenous infusion, bolus 5-FU (400 mg/m(2) on day 1), and then continuous infusion 5-FU (3000 mg/m(2) on day 1) over 46 hours. Cycles were repeated every 2 weeks.. Sixty patients were enrolled (median age, 52.5 years old). Of these, 65% patients had Eastern Cooperative Oncology Group performance status of grade 2. A median of 8 cycles was administered (range, 4-12). Fifty-five patients were evaluable for response. Two patients achieved a complete response and 28 patients achieved a partial response, producing an overall response rate of 50% by intent-to-treat analysis. The median duration of response was 6.4 months (95% CI, 5.14-7.60 months). Median progression-free survival and median overall survival were 7.7 months (95% CI, 6.5-8.9 months) and 14.3 months (95% CI, 9.4-19.1 months), respectively. Hematologic toxicity was mild; grade 3 neutropenia was noted in only 6.7% of patients. Alopecia was the most common nonhematologic toxicity in 51 patients (71.4%). Grade 3 alopecia occurred in 11 patients (18.3%).. Combination chemotherapy of biweekly paclitaxel followed sequentially by infusion leucovorin, bolus 5-FU, and continuous infusion 5-FU over 46 hours is effective and well tolerated in patients with advanced gastric cancer, especially in patients with poor performance status who cannot tolerate aggressive chemotherapy regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Peritoneal Neoplasms; Skin Neoplasms; Stomach Neoplasms; Survival Rate; Time Factors; Treatment Outcome

To evaluate the safety and efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2-positive advanced gastric cancer.. T Thirty-four patients with pathologically confirmed advanced gastric cancer, all positive for the human epidermal growth factor receptor 2 (HER2) as identified by immunohistochemistry and fluorescence in situ hybridization, were randomized into the test group and control group to for treatment with the combined regimen and the FOLFIRI regimen alone, respectively. FOLFIRI regimen was administered every 2 weeks for 2 to 4 cycles. Trsatuzumab was given intravenously on a weekly basis with an initial dose of 4 mg/kg and a subsequent dose of 2 mg/kg. All the patients were assessed for efficacy and toxicity of the treatments.. The overall response rate was 58.8% in the test group and 35.3% in the control group, with disease control rates of 88.2% and 64.7%, respectively, showing significant differences between the two groups (P<0.05). The most frequent grade I/II treatment-related adverse events included diarrhea, nausea/vomiting and neutropenia.. Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated for treatment of HER2-positive advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Receptor, ErbB-2; Stomach Neoplasms; Trastuzumab

Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients.. In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m(2)], fluorouracil [5-FU] [400 mg/m(2)] and folinic acid 400 mg/m(2) or 200mg/m(2) of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months.. Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5-56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4-46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment.. Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Male; Stomach Neoplasms

We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients.. Patients with untreated stage IV GC received paclitaxel 80 mg/m(2) as a 1-hour infusion, followed by 5-FU 600 mg/m(2) as a bolus infusion and L-leucovorin 250 mg/m(2) as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days. The primary endpoint was response rate.. Thirty-five patients were enrolled. The median age was 62 years (range 34-75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal metastasis. The confirmed response rate was 43% (95% CI 26-61) with 15 partial responses. Stable disease was observed in 16 (46%) patients. Median progression-free survival and overall survival were 6.8 months (95% CI 5.8-7.4) and 16.2 months (95% CI 10.0-22.8), respectively. Grade 3-4 adverse events were: neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy (11%).. FLTAX showed a desirable safety profile, and the efficacy against advanced GC was encouraging. FLTAX may be a good option for GC patients with deteriorated general condition, and a randomized clinical trial in such patients is currently underway.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Stomach Neoplasms

The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of KRAS (3%). The aim of the correlative tumour tissue studies was to investigate the relationship between EGFR gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.. Patients included in this correlative study (n = 39) were a subset of patients from the clinical phase II study. The association between EGFR gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. EGFR gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene CDH1 was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.. Our study showed a significant association between increased EGFR gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two CDH1 exon 9 missense mutations (A408V and D402H) were detected.. Our finding that increased EGFR gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.. Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cadherins; Cetuximab; ErbB Receptors; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Proto-Oncogene Proteins B-raf; Stomach Neoplasms; Survival Analysis; Vitamin B Complex

In this prospective pilot study, we assessed the efficacy and safety of the FOLFIRI regimen (irinotecan 180 mg/m², leucovorin 200 mg/m² d1 followed by bolus 400 mg/m² 5-fluorouracil (5-FU) and by a 46-h 2400 mg/m² 5-FU infusion, every 2 weeks) in patients with advanced esophageal or junctional adenocarcinoma. Twenty-nine patients were included. A complete response was obtained in 2 patients, a partial response in 7 patients (objective response rate 31.0%). Stable disease was obtained in 13 patients (disease control rate 75.9%). The median progression-free and overall survivals were 5.9 and 8.6 months, respectively. One patient died from chemotherapy-related diarrhea after one cycle but this patient presented concomitant disease progression with cerebral metastases. We observed one additional grade 4 diarrhea, one grade 3 vomiting, and two grade 3 neutropenias. To conclude, FOLFIRI regimen appears quite active, with an acceptable safety profile in patients with advanced esophageal or junctional adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Prospective Studies; Stomach Neoplasms

This study evaluated the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil/leucovorin as neoadjuvant chemotherapy before surgery (NCT group; n = 29) compared with postoperative chemotherapy alone (non-NCT group; n = 26) in the treatment of Borrmann type IV gastric carcinoma. Primary tumour response rate, surgical parameters, incised-edge residue rate, lymphatic metastasis status and side-effects were evaluated. The overall response rate was 58.6% in the NCT group, which included three (10.3%) patients in complete remission and 14 (48.3%) patients in partial remission. The postoperative pathological complete response rate was 6.9% (two patients) in the NCT group. NCT was associated with a significant increase in the radical resection rate and a significant decrease in the rate of incised-edge residues, compared with postoperative chemotherapy alone. Side-effects due to NCT were minimal and resolved with appropriate treatment. There were no chemotherapy-related deaths in either group. In conclusion, docetaxel, cisplatin and 5-fluorouracil/leucovorin was an effective and well-tolerated NCT regimen for Borrmann type IV gastric cancer.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Stomach Neoplasms; Taxoids; Treatment Outcome

The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric (GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m(2) docetaxel or 180 mg/m(2) irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were reasonably well tolerated. Grade 3-4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and appears active in advanced UGIA.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Camptothecin; Digestive System Neoplasms; Docetaxel; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Pancreatic Neoplasms; Quality of Life; Stomach Neoplasms; Taxoids; Treatment Outcome; Vitamin B Complex

The primary objective of this trial was to evaluate the response rate for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the treatment of advanced gastric cancer in a phase II, cooperative group setting.. Patients with locally advanced, unresectable, or metastatic adenocarcinoma of the stomach received trimetrexate 110 mg/m IV over 60 minutes day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours x 7 doses, all weekly for 6 weeks followed by 2 weeks of rest, continued until progression.. Characteristics for 37 eligible patients: median age 63 (range: 23-83); male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response rate was 19%, and median overall survival was 6 months. Two patients died as a result of therapy, 1 because of infection without significant neutropenia, and 1 due to perforation of a responding gastric lesion. Seventy-two percent experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and lymphopenia.. This regimen achieves response rates comparable to other 5-FU-based regimens, when used in treatment of incurable gastric cancer. Toxicity appears manageable.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Survival Rate; Treatment Outcome; Trimetrexate; Young Adult

To determine the activity and toxicities of a low-dose leucovorin plus 5-fluorouracil (5-FU) regimen, combined with irinotecan and administered every 2 weeks (modified FOLFIRI), as a first-line therapy for patients with advanced gastric cancer.. Patients were treated with cycles of 150 mg/m irinotecan on day 1 plus 50 mg of LV, followed by a 400 mg/m 5-FU bolus and a 22-hour continuous infusion of 600 mg/m 5-FU on days 1 and 2.. The median patient age was 55 years (range, 29-75 years), and 77% (34/44) of the patients had a performance status (Eastern Cooperative Oncology Group) of 0 or 1. Of the 44 patients evaluated for their tumor response, 3 patients (6.8%) and 14 patients (31.8%) achieved a complete and partial response, respectively, with an overall response rate of 38.6% (95% confidence interval, 23.7%-53.6%). 13 patients (29.6%) evidenced a stable disease, and 14 patients (31.8%) progressed during the course of the treatment. The median time to progression and overall survival time were 4.9 months (range, 0.9-22.8 months) and 10.3 months (range, 1.2-29.0 months) from the start of the chemotherapy, respectively. A total of 293 cycles were assessed for toxicity. The major hematologic toxicities included grade 1 to 2 anemia (27.6%), neutropenia (48.8%), and grade 3 to 4 neutropenia (12.6%). There were 7 cycles of neutropenic fever. Nonhematological toxicities were observed grade 3 vomiting (6.8%), grade 3 diarrhea (4.5%), and grade 3 mucositis (2.3%). We noted no treatment-related deaths.. The modified FOLFIRI regimen-lowering of irinotecan and LV doses-is a safe and feasible regimen as a first-line therapy for patients with recurrent or metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Gastrointestinal Diseases; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Treatment Outcome

A phase II study was carried out to assess the efficacy and toxicity of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) for the treatment of patients with metastatic or recurring gastric cancer previously treated with fluoropyrimidine-based chemotherapy.. Eligible patients were those who had metastatic gastric cancer previously treated with a fluoropyrimidine-based chemotherapy regimen or had disease recurrence within 6 months of completing adjuvant fluoropyrimidine-containing chemotherapy. Participants received irinotecan (150 mg/m² on day 1) and leucovorin (LV; 20 mg/m² on days 1-2) followed by continuous infusion of 5-FU (1500 mg/m² on days 1-2), every 2 weeks.. Between April 2006 and March 2008, 33 patients were enrolled in the study. FOLFIRI served as a second-line treatment in 27 patients, third-line treatment in 4 patients, and fourth-line treatment in 2 patients. The patients had a median age of 60 years (range, 40-75) and underwent 132 cycles of chemotherapy, with a median of 3 cycles (range, 1-15) per patient. The response rate was 18.2%, and the disease control rate was 36%. Median overall survival was 5.1 months (95% confidence interval, 3.74-6.45), and median time to progression was 2.3 months (95% confidence interval, 1.81-2.78). The major grade 3-4 toxicity was neutropenia (45.4%).. Combination chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients previously treated with fluoropyrimidine-based chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Risk Assessment; Salvage Therapy; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR). The present study investigated the association between germline genetic polymorphisms and the treatment outcome of cetuximab plus modified leucovovin, fluorouracil, and oxaliplatin (FOLFOX)6 chemotherapy in advanced gastric cancer (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16 polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth factor-alpha (TGFA), thymidylate synthase, excision repair cross-complementation group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival. Twenty-one patients had low repeats (sum of both alleles or=38). Patients with low CA repeats had longer progression-free survival (adjusted hazard ratio [HR] 0.42 [95% confidence interval [CI] 0.19-0.96], P = 0.040) and overall survival (adjusted HR 0.40 [95% CI 0.16-0.99], P = 0.048) compared with patients with high CA repeats. In addition, the tumor EGFR expression was higher in patients with a lower number of CA repeats. The association between the CA repeat status and survival was not found in a separate cohort of AGC patients (n = 68) treated only with modified FOLFOX6. These results suggest that the EGFR intron 1 CA repeat polymorphism could be a useful, predictive biomarker of cetuximab efficacy in AGC and merits further investigation in randomized studies.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Dinucleotide Repeats; ErbB Receptors; Female; Fluorouracil; Genotype; Humans; Introns; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Polymorphism, Genetic; Stomach Neoplasms

Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.. Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m(-2) at first infusion followed by weekly infusions of 250 mg m(-2) combined with FUFOX (oxaliplatin 50 mg m(-2), 5-FU 2000 mg m(-2), and DL-folinic acid 200 mg m(-2) d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.. Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.. Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mutation; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Stomach Neoplasms

Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin-based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin).. Lipoplatin was given at a dose of 120 mg/m(2)/week, 5-fluorouracil at 400mg/m(2)/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively.. Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles.. Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fatigue; Feasibility Studies; Female; Fluorouracil; Humans; Kidney; Leucovorin; Male; Middle Aged; Neutropenia; Radiation Tolerance; Radiotherapy Dosage; Stomach Neoplasms

5-Fluorouracil (5-FU) plus cisplatin (C) can be considered a standard option for advanced gastric cancer (AGC). Irinotecan (Ir) and docetaxel (D) are active agents with no complete cross-resistance with C and 5-FU. Concomitant combination of Ir or D with C and 5-FU is feasible, but with substantial toxicities. A different way to include all active agents in first-line treatment of AGC may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with 5-FU-based doublets with C, Ir and D in the first-line treatment of AGC.. We conducted a phase II study of first-line sequential chemotherapy in metastatic GC. Treatment consisted of 3 cycles of C + infused 5-FU and leucovorin (CFL) followed by 3 cycles of Ir + 5-FU/LV (IrFL) followed by 3 cycles of D + 5-FU/LV (DFL). Primary end-point was response rate.. Forty-six patients were enrolled, median age 60 years, sites of disease (single/multiple) = 9/37, PS 0/1 = 27/19, gastric/gastro-oesophageal junction = 39/7. Median number of cycles was 9. Main grade 3-4 toxicities were neutropenia (37%), febrile neutropenia (2%), diarrhoea (4%), stomatitis (9%). Response rate after the planned 9 cycles was 45% (15 partial and 5 complete responses among 43 evaluable patients). Median PFS and OS: 6.8 and 11.1 months, respectively.. This sequential treatment is feasible with a favourable safety profile and produced encouraging results in terms of activity and efficacy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms; Taxoids; Treatment Outcome

To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin.. This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups.. Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar.. This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Calcium Gluconate; Colorectal Neoplasms; Double-Blind Method; Drug Therapy, Combination; Female; Fluorouracil; Glutathione; Humans; Infusions, Intravenous; Leucovorin; Magnesium Sulfate; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Stomach Neoplasms; Young Adult

The present study evaluated the efficacy and safety of oxaliplatin, UFT, and leucovorin in metastatic gastric cancer.. Patients received intravenous oxaliplatin 130 mg/m(2) on day 1, followed by oral UFT capsules (350 mg/m(2) per day) and leucovorin tablets (90 mg/day), every 8 h, for 14 days, in a 3-week cycle.. Twenty-three patients (61% with > or = 2 metastatic sites), median age of 60 years (range, 39-69 years) were entered. Based on intention-to-treat analysis, one complete response and seven partial responses were found, resulting in an overall response rate (RR) of 35% (95% confidence interval [CI], 16-54), a median time to progression of 4 months (95% CI, 0.5-7.5), and a median overall survival (OS) of 8 months (95% CI, 4.5-11.5). The 1-year survival rate was 26%. Three patients did not complete the first course of 2 weeks; 1 died suddenly on day 16 with fatal lung embolism; 1 had rapid progressive disease and 1 experienced gastric hemorrhage on day 15 - both these patients withdrew. In the 20 patients assessable for toxicity no grade 4 toxicity occurred, grade 3 toxicity consisted of anemia in 1, diarrhea in 2, and neurotoxicity in 3 patients. No hand-foot syndrome (HFS) occurred.. Oxaliplatin is an effective drug in gastric cancer, but, as previously reported, its feasibility in combination with capecitabine is hampered due to combined hand-foot-based toxicity. The present phase II study of a combination of oxaliplatin with UFT and leucovorin appears to have efficacy and tolerability comparable to two other drug regimens used in gastric cancer, without the HFS problem.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival; Tegafur; Treatment Outcome; Uracil

Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy. We evaluated the potential of FDG-PET for the assessment of response and prognosis in the multimodality treatment of gastric cancer.. Study patients were recruited from a prospective observation trial. Forty two patients with advanced gastric cancer received neoadjuvant chemotherapy and subsequently 40 patients underwent standardized gastrectomy (2 patients with tumor progression had therapy limited to palliative chemotherapy without surgery). Histomorphologic regression was defined as major response when resected specimens contained <10% vital tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV (SUV2); percentage change (SUVDelta%)].. Histomorphological tumor regression was confirmed as a prognostic factor (P = 0.039). No significant correlations between SUV1, SUV2, or SUVDelta% and response or prognosis were found.. FDG-PET seems not to be an imaging system that effectively characterizes major/minor response and survival in patients with gastric cancer following multimodality treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorodeoxyglucose F18; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Stomach Neoplasms

The optimal chemotherapy in patients with advanced gastric carcinoma (GC) is yet to be determined. We compared sequential administration of docetaxel and irinotecan, both in combination with infused 5-fluorouracil/leucovorin (5-Fu/Lv), and randomly assigned patients to start with either of the two.. Patients with previously untreated locally advanced or metastatic GC and with measurable lesions (response evaluation criteria in solid tumors; RECIST) were randomly assigned to start with docetaxel 45 mg/m(2) (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus/44-h infusion of 5-Fu/Lv (day 1 every 2 weeks). After four courses, there was a prescheduled crossover to the alternative regimen for four additional courses.. Eighty-one patients were randomized and 78 started treatment. Complete and partial responses were seen in 31 (40%) patients after 8 weeks and in 32 (41%) after 16 weeks, with similar results in both study arms. The median overall survival (OS) was 11.5 and 10.6 months in arms T and C, respectively (P = 0.3). The two schedules were feasible and did not differ in the overall rate of severe adverse events (SAEs).. This is the first randomized comparison of two of the newer cytostatic drugs in GC therapy. No differences favoring either arm T or arm C were found with respect to response rate, OS, or toxicity. The median OS of 11 months indicates that sequential administration of the two combinations is effective and is similar to triple combinations. Thus, comparable efficacy to platinum combinations appears to be obtained with newer, less toxic regimens when given sequentially.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Docetaxel; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Statistics as Topic; Stomach Neoplasms; Surveys and Questionnaires; Survival Analysis; Taxoids; Time Factors; Vitamin B Complex

To evaluate the clinical efficacy and the toxicity of neoadjuvant chemotherapy with paclitaxel and FOLFOX4 (5-fluorouracil/leucovorin combined and oxaliplatin) regimen for advanced gastric cancer.. Seventy-eight patients with cTNM stage III or IV (M0) gastric cancer were enrolled and 39 were randomized into the treatment arm (n=39, paclitaxel combined with FOLFOX4 regimen neoadjuvant chemotherapy every two weeks in each cycle) and control group (n=39). Clinical response was evaluated with RECIST criteria after 3 cycles. Patients in experimental group received surgery after 2-4 weeks and postoperative chemotherapy of 3 cycles of the original regimen. When disease progressed, postoperative chemotherapy regimen was changed into ECF regimen. The control group of 39 patients received surgery within 2 weeks and postoperative chemotherapy of 6 cycles of paclitaxel combined with FOLFOX4 regimen.. The clinical response rate was 66.7% in the treatment arm. The R0 resection rate (59.0%) was significantly higher than that in the control group (P=0.025) and the number of lymph node metastasis in the treatment arm(3.23±2.80) was significantly lower than that in the control group (5.79±2.69, P=0.001). There were no significant differences in postoperative complication rate (5.1% vs. 2.6%) and the number of lymph node dissection (19.69±2.95 vs. 20.59±3.22) between the two groups (P>0.05). The median survival time and 2-year survival rate in the treatment arm [(27.10±2.32) months and 59.0%] was significantly higher than that in the control group[(18.20±1.30) months and 28.2%] (P=0.001, P=0.006). Cox regression multivariable analysis showed that tumor differentiation, R0 resection, lymph node metastasis were independent prognostic factors. Adverse reaction of chemotherapy, mainly hematological adverse reactions, and peripheral nerve toxicity, were tolerable. No significant differences were noted between the two groups in adverse reactions (P>0.05).. The efficacy of paclitaxel combined with FOLFOX4 as neoadjuvant chemotherapy is high. Patients tolerance and compliance are satisfactory. It can improve in patients with advanced gastric cancer the R0 resection rate, reduce lymph node metastasis and improve survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Stomach Neoplasms

Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression.. Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m(-2), followed by cisplatin 30 mg m(-2) infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m(-2) per day plus leucovorin 90 mg per day on days 1-14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment.. From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22-75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41-74%) and 53% (95% CI: 38-68%), respectively. The disease control rates in these populations were 85% (95% CI: 70-94%) and 82% (95% CI: 68-92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3-4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities.. Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Administration Schedule; Female; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms; Taxoids; Tegafur; Uracil

Advanced esophagogastric carcinoma has a poor prognosis. Palliative chemotherapy provides a survival advantage and improved quality of life. Epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) is a well-established chemotherapy regimen but a continuous chemotherapy infusion is not always feasible or acceptable.. We conducted a phase I and II trial of a modified version of ECF, utilizing 5-FU as a 24-h infusion on day 1 and day 8 of a 21-day cycle, administered with sodium folinate as a modulator of 5-FU (ECSF). In the phase I study the dose of 5-FU was increased in successive cohorts from 1250 mg/m(2) , 1500 mg/m(2) , and 1750 mg/m(2) to 2000 mg/m(2) per 24 h.. Dose limiting toxicity of febrile neutropenia was encountered at 2000 mg/m. The recommended dose for 5-FU was 1750 mg/m(2) . Overall 29 patients were treated with ECSF of whom 27 were evaluable for toxicity. The response rate was 45% on an intention-to-treat analysis with a complete response rate of 3%. The median response rate was 4.1 months and the median survival was 10.7 months. A total of 23 patients (72%) obtained clinical benefit with improvement in dysphagia or weight gain. central venous catheter (CVC) complications were observed in 12 (41%) patients.. ECSF was associated with a response rate and survival similar to that reported with standard ECF. ECSF may provide an alternative regimen to standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. CVC complications are a limitation.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Therapy, Combination; Epirubicin; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Rate; Treatment Outcome; Vitamin B Complex

The current study assessed the efficacy and safety of biweekly oxaliplatin combining oral tegafur-uracil/leucovorin in treating chemonaive patients with advanced gastric cancer.. Eligible patients were 18-75 years old, had stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0-2. Patients in the current study received 2-h i.v. infusion of oxaliplatin at a dose of 100 mg/m(2) after diluting in 500 mL 5% dextrose/water (dexan premedication), and 5-HT3 antagonist biweekly. Oral tegafur-uracil and leucovorin was given at a dose of 300 mg/m(2)/day and 60 mg/day three times daily from day 1 to 21, respectively, followed by a 1-week rest. Response assessment was based on the RECIST criteria and was performed every two courses. Toxicity was assessed according to NCI common toxicity criteria version 2.. From October 2003 to April 2006, 57 patients were evaluated (55 eligible) with a median age of 61 years (range 31-75). According to the assessment of response in 48 evaluable patients, partial response rate was 24/48 (50.0%) (95% CI: 35.23-64.73%) and stable disease was observed in 11 patients (22.92%), and diseased progressed in 13 patients (27.08%). Mean number of oxaliplatin cycles was 3 (0.5-6.5). Median time to progression was 177 days. Median overall survival was 318 days. Major-grade (III/IV) toxicities were diarrhea 25.5%, vomiting 16.5%, anemia 10.9%, numbness 12.7%, thrombocytopenia 7.3%, neutropenia 3.6% and leucopenia 1.8%.. Biweekly, oxaliplatin combining oral tegafur-uracil/leucovorin in treating patients with advanced gastric cancer showed acceptable activity and manageable toxicity.

Topics: Adenocarcinoma; Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome; Uracil; Young Adult

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cetuximab; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Advanced or metastatic gastric cancer, which is one of the most common malignancies in Korea, is difficult to cure by surgery alone and generally requires combination chemotherapy. Paclitaxel is active against gastric cancer and when combined with 5-fluorouracil/leucovorin and/or cisplatin is effective in the treatment of gastric cancer. We attempted to determine the effect and safety with the combination of paclitaxel with split cisplatin and 5-fluorouracil/leucovorin in advanced or metastatic gastric cancer. Patients with histologically-proven locally advanced/metastatic or recurrent gastric cancer with an ECOG performance status 0-2 were enrolled. The patients received 135 mg/m(2) of paclitaxel as a 3-h intravenous infusion on day 1 and 5-fluorouracil (1200 mg/m(2)) plus leucovorin (20 mg/m(2)) as an intravenous infusion over 12 h plus cisplatin (30 mg/m(2)) by continuous intravenous infusion on days 1-3, every 21 days. Between September 2003 and April 2005, 30 patients (26 evaluable patients) with a median age of 57 years (range 34-74) were enrolled and underwent 111 completed treatment cycles (a median of 3 cycles per patient). Of the evaluable patients, 12 patients showed a partial response and 8 patients had stable disease. The overall response rate was 46.2%. The median progression-free survival was 5.6 months (95% CI. 3.76-7.4 months), and the median overall survival was 9.6 months (95% CI. 6.67-12.47 months). The hematologic and non-hematologic toxicities were tolerable. The grade III and IV hematologic toxicities were anemia (6.8%) and neutropenia (2.6%). Febrile neutropenia was observed in 1 patients and 1 cycle. Other hematologic toxicities and grade III and IV non-hematologic toxicities, except nausea (66.7%) and vomiting (33.3%) were uncommon and not severe. TPFL combination chemotherapy is effective and tolerable with acceptable toxicities in patients with advanced/metastatic, recurrent gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Paclitaxel; Salvage Therapy; Stomach Neoplasms; Treatment Outcome

The efficacy of chemotherapy for advanced gastric cancer with palliative intent compared with supportive care alone is now widely accepted. However, the best choice of chemotherapy regimen for patients with advanced gastric cancer is still a matter of controversy and requires further investigation. This study is performed to evaluate the efficacy and safety of the FOLFOXIRI regimen (oxaliplatin 85 mg/m as a 2-h intravenous infusion, irinotecan 165 mg/m as a 90-min infusion, leucovorin 200 mg/m as a 2-h infusion, 5-fluorouracil 3200 mg/m as a 48-h continuous infusion on day 1, every 2 weeks) as first-line treatment for advanced gastric cancer. Forty-seven (95.9%) of the 49 patients were assessable for response. Two cases of complete response and 29 cases of partial response were confirmed, giving an overall response rate of 63.3% [95% confidence interval (CI): 49.8-76.8%]. The median time to progression and overall survival for all patients were 7.3 months (95% CI: 6.0-8.6 months) and 11.9 months (95% CI: 9.4-14.4 months), respectively. The estimate of overall survival at 12 months was 42.9% (95% CI: 29.0-56.7%). Most patients experienced neutropenia during their course of therapy with 49% of patients (n=23) for grade 3/4 neutropenia. Grade 3 nausea/vomiting, stomatitis, and diarrhea were observed in 20 (42.6%), two (4.3%), and five (10.6%) patients, respectively. Yet, no grade 4 nonhematologic toxicity was observed. The FOLFOXIRI combination is a tolerated treatment modality with promising activity in previously untreated advanced gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Stomach Neoplasms; Survival Rate; Treatment Outcome; Young Adult

This phase II trial assessed the tolerability and efficacy of a triplet of oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer.. Patients with unresectable or metastatic gastric cancer, unexposed to palliative chemotherapy, received oxaliplatin 85 mg/m(2) iv and irinotecan 150 mg/m(2) iv on day 1, 6S-folinic acid 250 mg/m(2) iv and fluorouracil 750 mg/m(2) iv on day 2, every 2 weeks. Response rate (RR) was assessed after a minimum of four cycles, and treatment continued up to 12 cycles.. Sixty-three patients were treated, with a median of eight (range 1-12) cycles/patient. Two complete and 19 partial responses were registered (RR 33% [95% CI, 22-46%]). Median progression-free survival was 7.5 (95% CI, 5.6-9.4) months, and median overall survival was 12.1 (95% CI, 10.8-13.4) months. Most common grade > or =3 toxicities were neutropenia (59%), febrile neutropenia (7%), vomiting (20%), and diarrhoea (10%). All-grade neurotoxicity affected 33% of patients.. Oxaliplatin, irinotecan, and fluorouracil/folinic acid administered every 2 weeks are safe and active in advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Camptothecin; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Tomography, X-Ray Computed

The aim of this study was to evaluate the efficacy and safety of biweekly oxaliplatin in combination with continuous infusional 5-fluorouracil and leucovorin (modified FOLFOX regimen) in elderly patients with advanced gastric cancer (AGC). Forty-six eligible patients older than 65 years with previously untreated AGC received oxaliplatin 85 mg/m intravenously over a 2-h period on day 1, together with leucovorin 400 mg/m over 2 h, followed by a 46-h infusion of 5-fluorouracil 2600 mg/m every 2 weeks. All patients were evaluable for efficacy and toxicity. A median of seven cycles (range 1-12) was administered. The overall response rate was 45.6% [95% confidence interval (CI): 31-61%] with two complete responses, 19 partial responses, 15 stable diseases, and 10 progressions. Median time to progression was 6.2 months (95% CI: 4.6-7.8) and median overall survival was 9.8 months (95% CI: 8.2-11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (8.7%), nausea (4.3%), vomiting (4.3%), diarrhea (2.2%); and grade 4 toxicities occurred in none of the patients. Grades 1-2 peripheral neuropathy was reported in 43.5% of patients. The modified FOLFOX regimen is active, well tolerated as first-line chemotherapy for elderly patients aged above 65 years with AGC.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Neutropenia; Organoplatinum Compounds; Peripheral Nervous System Diseases; Stomach Neoplasms; Survival Rate; Treatment Outcome

Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer. We attempted to determine whether single nucleotide polymorphisms in ERCC1, GST, TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Total genomic DNA was extracted from the whole blood of patients. The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1, GST, TS and UGT1A1. The response rate of FOLFOX (N=75) was 24%. Grade 3-4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16%, respectively. TTP and OS of first-line administration of FOLFOX (N=35) were 3.1 months (95% CI, 0.1-6.1 months) and 13.9 months (95% CI, 12.2-15.6 months), respectively. Only the GSTM1 positive genotype exhibited a significantly better time to progression (P=0.023). However, significant genotypic variation of TS, GST and ERCC1, which was assumed to affect the activity of oxaliplatin, was not observed to affect RR, toxicity and overall survival. The response rate of FOLFIRI (N=74) was 23%. Grade 3-4 neutropenia and diarrhea were observed in 55.4 and 9.5% of cases, respectively. TTP and OS of first-line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5-6.4 months) and 19.0 months (95% CI, 8.5-29.5 months). The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia. However, significant genotypic variation of UGT1A1, which was assumed to affect irinotecan toxicity, was not observed to affect RR, toxicity or survival. In this study, the GSTM1 positive genotype evidenced a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX. The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Frequency; Genotype; Glucuronosyltransferase; Glutathione Transferase; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Patient Selection; Phenotype; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Predictive Value of Tests; Stomach Neoplasms; Thymidylate Synthase; Time Factors; Treatment Outcome

To evaluate the efficacy and safety of the combination of oxaliplatin and ELF (VP16/CF/5-Fu) regimen in the treatment of patients with advanced gastric cancer.. Oxaliplatin was given at a dose of 100 mg/m(2) i.v. 2 hours D1, calcium folinate (CF) 200 mg/m(2) i.v. 1/2 hour D1 approximately D3, 5-fluorouracil (5-Fu) 500 mg/m(2) i.v. 2 hours D1 approximately D3 and etoposide 100 mg/m(2) i.v. 3 hours D1 approximately D3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 2 cycles.. Sixty-nine patients were enrolled into the study. All cases were pathologically confirmed as gastric cancer (adenocarcinoma in 57 cases and signet ring cell carcinoma in 12 cases). 42 patients had newly diagnosed disease, and 27 patients had received previous chemotherapy. 62 patients were analyzed for response (7 complete responses and 25 partial responses) with total response rate 51.61%. The median time to progression was 5.7 months and the median overall survival was 9.2 months. The most common hematologic toxicities were anemia (29.0%), leucopenia (51.2%) and thrombocytopenia (21.2%). No grade 4 and grade 5 hematologic toxicities were observed. The most common non-hematologic toxicities were nausea (46.5%), vomiting (41.1%), peripheral sensory neuropathy (47.1%), and grade 2 alopecia (27.3%).. This oxaliplatin combined with ELF regimen shows good efficacy and acceptable safety in advanced gastric cancer patients. It is worthy to be proved as a suitable alternative regimen in this indication.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented.. Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling.. A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm.. There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Esophagogastric Junction; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Neoplasm Metastasis; Palliative Care; Quality of Life; Stomach Neoplasms; Young Adult

The aim of this study is to investigate the efficiency and toxicity of the FOLFOX regimen, the combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and calcium folinate (CF), for patients with locally advanced or metastatic gastric cancer.. Ninety-six patients with locally advanced or metastatic gastric adenocarcinoma, including 72 males and 24 females, were treated with FOLFOX regimen: L-OHP 85 mg/m(2) iv in 2 hours on D1, CF 200 mg/m(2) iv in 2 hours on D1 and D2, 5-Fu 400 mg/m(2) iv on D1 and D2, and then continuous infusion of it at a dose of 600 mg/m(2) for 44 hours. This regimen was repeated every 2 weeks. The first evaluation was done after four cycles. The median cycle of the chemotherapy was 6 (range: 1 to 12 cycles).. Of the 96 patients with gastric cancers, 21 underwent R0 resection and afterward received adjuvant FOLFOX chemotherapy. Ten of those were still alive, while the other 11 died of the disease, with a median disease free survival time of 24.0 months and 3-year survival rate of 51.8%. The other 75 received only palliative chemotherapy due to non-operable advanced disease. Thirty of those achieved partial response (PR), the other 20 had a stable disease (SD), but the remaining 25 experienced disease progression (PD), with an overall response rate of 40.0%. The median TTP and overall survival in those 75 patients was 5.9 and 12.0 months, respectively. All 96 patients were evaluable for toxicity according to NCI criteria. The patients of grade 3 vomiting and neural toxicity were 6 and 4, respectively.. In terms of efficacy and safety, the FOLFOX regimen is effective and well tolerable for patients with locally advanced or metastatic gastric cancers either as adjuvant or palliative chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Remission Induction; Stomach Neoplasms; Survival Rate; Vomiting

To investigate the efficiency, time to progression (TTP), overall survival (OS) and toxicity of epirubicin combined with DDP and 5-Fu (PELF regimen) for the treatment of advanced gastric cancer.. Totally, 101 patients with histopathologically confirmed advanced gastric cancer were enrolled and treated with PELF regimen in this study. Among them, 37 cases received adjuvant chemotherapy after R0 resection and 64 cases only received palliative chemotherapy without surgical resection. The regimen comprised of intravenous (i.v.) administration of epirubicin 50-80 mg/m2 for palliative chemotherapy or 40-50 mg/m2 for postoperative adjuvant chemotherapy on D1; i.v. infusion of cisplatin 10-20 mg/m2 in 2 hours on D1-D5; i.v. infusion of 5-Fu 425-600 mg/m2 for palliative chemotherapy or 425-500 mg/m2 for adjuvant chemotherapy in 4 hours for 5 days or continuous infusion for 120 hours; i.v. infusion of leucovorin (LV) 100-200 mg/m2 in 2 hours on D1-D5. This regimen was repeated every 3 to 4 weeks, and the first evaluation was done after two cycles.. Of the 37 patients who received adjuvant chemotherapy after R0 resection, 17 were still alive without recurrence, while 19 died of the disease. The median disease free survival time was 36.1 months and 5-year survival rate was 36.0%. Among the 64 cases who received only palliative chemotherapy, 47 patients were treated with this regimen as a first-line therapy and 34 patients were evaluable for response. The overall response rate was 26.5%, median time to progression (TTP) and overall survival (OS) was 6.6 and 13.7 months, respectively. Of the 17 patients who received this regimen as a second-line therapy, 10 were evaluable with an overall response rate of 20.0%. The median time to progression (TTP) in patients of this group was 5.1 months and median overall survival (OS) was 8.9 months. All the 101 patients were assessable for toxicity according to WHO criteria. The rate of grade 3 or 4 neutropenia, anemia and thromobocytopenia was 19.8%, 1.0% and 2.0%, respectively.. The regimen of epirubicin combined with DDP and 5-Fu is effective, well tolerable and safe for advanced gastric cancer patients either as adjuvant or as palliative therapy.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Disease-Free Survival; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neutropenia; Palliative Care; Retrospective Studies; Stomach Neoplasms; Survival Rate; Thrombocytopenia

The standard of care for metastatic gastric cancer (MGC) is systemic chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3 years is rare. For selected groups of patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and metastasectomies including peritoneal stripping with continuous hyperthermic peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median survival after liver resection for MGC is up to 34 months, with a five year survival rate of 24.5%. Similarly, reported median survival after pulmonary resection of MGC is 21 months with long term survival of greater than 5 years a possibility. Several case reports and small studies have documented evidence of long-term survival in select individuals who undergo CHPP for MGC.. The GYMSSA trial is a prospective randomized trial for patients with MGC. It is designed to compare two therapeutic approaches: gastrectomy with metastasectomy plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA). Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study is to evaluate overall survival and potential selection criteria to determine those patients who may benefit from surgery plus systemic therapy. The study will be conducted by the Surgery Branch at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup will be done at the NCI, and chemotherapy will be given by either the local oncologist or the medical oncology branch at NCI.. ClinicalTrials.gov ID. NCT00941655.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Fluorouracil; Gastrectomy; Hepatectomy; Humans; Hyperthermia, Induced; Leucovorin; Organoplatinum Compounds; Peritoneum; Pneumonectomy; Stomach Neoplasms; Survival Rate

To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer.. Chemonaive patients with histologically confirmed advanced or recurrent inoperable gastric cancer were enrolled in the present study. Treatment consisted of paclitaxel (75 mg/m(2)) and leucovorin (40 mg/m(2)) as a 2-h intravenous infusion, followed by 5-fluorouracil (2,400 mg/m(2)) as a 46-h continuous infusion. Cycles were repeated every 2 weeks.. Thirty patients were enrolled in this study. There were 12 partial responses, giving an overall response rate of 40.0%. At a median follow-up of 10.6 months, the median time to progression and median overall survival were 3.9 and 8.8 months, respectively. The most common hematological toxicity was grade 1-2 anemia, which was seen in 83.3% of patients. No grade 4 leukopenia, thrombocytopenia, or anemia was noted. The most common non-hematological toxicity was anorexia, which was seen in 70% of patients, although grade 3 anorexia was noted in only 10% of cases. There was no severe treatment-related morbidity or death.. Combination chemotherapy consisting of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin was effective and well tolerated in patients with advanced gastric cancers.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Paclitaxel; Recurrence; Stomach Neoplasms; Survival Analysis

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Survival Rate; Taiwan; Treatment Outcome

As prognosis of advanced gastric cancer is still poor, a standard regimen after first-line fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer.. Treatment consisted of weekly doses of MTX (100 mg/m(2), i.v. bolus), followed by 5-FU (600 mg/m(2), i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m(2), given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate.. Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20-75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0-20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%.. Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Drug Administration Schedule; Female; Fluorouracil; Humans; Injections, Intravenous; Japan; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Neutropenia; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Vitamin B Complex

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin (OXA) in combination with continuous infusional 5-fluorouracil (5-FU) and leucovorin (LV) administered every 2 weeks (modified FOLFOX-4 regimen) in elderly patients with advanced gastric cancer (AGC).. A total of 44 previously untreated AGC patients aged 65 or older were treated with OXA 85 mg m-2 on day 1, LV 200 mg m-2 as a 2-hour infusion followed by a 22-hour infusion of 5-FU 1000 mg m using a multichannel programmable pump, repeated for 2 consecutive days every 2 weeks.. All patients were assessable for toxicity and 40 patients for response. Median age was 69 years (65-83). The response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 52.5% (95% confidence interval: 44.6%-68.0%) with 3 complete responses, 18 partial responses, 11 stable diseases, and 8 progressions. Median time to progression was 6.5 months and median overall survival was 10.0 months. Toxicity was generally mild. Grade 3 hematologic toxicities of neutropenia, anemia, and thrombocytopenia were in 6.8%, 2.3%, and 4.5% of the patients, respectively. No grade 4 hematologic toxicities occurred. Grade 1 peripheral neuropathy was a common event (34.1%), whereas grade 3 peripheral neuropathy was recorded in only 1 (2.3%) patient. An acute hypersensitivity reaction was observed in 1 patient during administration.. The modified FOLFOX-4 regimen is an active and well-tolerated chemotherapy for elderly patients aged > or =65 years with AGC. OXA may occasionally cause mild hypersensitivity.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Hypersensitivity; Female; Fluorouracil; Follow-Up Studies; Granisetron; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Premedication; Stomach Neoplasms; Survival Rate; Treatment Outcome

We investigated whether the level of bone marrow-derived progenitor cells and mature endothelial cells could be used as predictors of clinical outcome in patients receiving taxotere-based chemotherapy for advanced gastric cancer. Peripheral blood mononuclear cells were obtained from 49 gastric cancer patients who received taxotere combined with 5-FU and leucovorin and prophylactic G-CSF treatment. To categorize the cells, the cell markers CD34, vWF, P1H12, and CD31 were stained. Changes in these cells were examined before and after chemotherapy, and the clinical significance of these changes to response prediction and prognosis were investigated. Before the second cycle of chemotherapy, the number of CD34+/vWF+ and CD34+ cells was higher in non-responders as compared to the responders. Patients with > or =6.2 CD34+/vWF+ cells/ml had a shorter progression free survival (3.7 months) as against patients with <6.2 CD34+/vWF+/ml (6.0 months, p = 0.076). Patients with > or =5.8 CD34+ cells/ml had shorter progression free survival (4.0 months) than patients with <5.8 CD34+ cells/ml (6.1 months, p = 0.046). In an ex vivo pharmacokinetic study, the maximum inhibition (I(max)) for HUVEC and YCC3 cells was 13.0 +/- 6.6% and 74.0 +/- 2.0%, respectively. The time to reach I(max) (T(max)) was 72 h in all HUVEC cells and 0.5 hours in YCC3 cells. We suggested that CD34+/vWF+ and CD34+ cells can be used as a biomarker for prediction and CD34+ cells for prognosis.

Topics: Adenocarcinoma; Adult; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone Marrow Cells; Cell Line, Tumor; Cell Movement; Cell Survival; Cells, Cultured; Disease-Free Survival; Docetaxel; Endothelial Cells; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Stem Cells; Stomach Neoplasms; Taxoids; Time Factors; Treatment Outcome

We aimed to establish the superiority (or noninferiority if superiority was not achieved) in terms of time to progression (TTP) of irinotecan/5-fluorouracil (IF) over cisplatin/5-fluorouracil (CF) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction.. Patients received either IF: i.v. irinotecan 80 mg/m(2) 30 min, folinic acid 500 mg/m(2) 2 h, 5-fluorouracil (5-FU) 2000 mg/m(2) 22 h, for 6/7 weeks or CF: cisplatin 100 mg/m(2) 1-3 h, with 5-FU 1000 mg/m(2)/day 24 h, days 1-5, every 4 weeks.. In all, 333 patients were randomized and treated (IF 170, CF 163). Patient characteristics were balanced except more IF patients had Karnofsky performance status 100%. TTP for IF was 5.0 months [95% confidence interval (CI) 3.8-5.8] and 4.2 months (95% CI 3.7-5.5) for CF (P = 0.088). Overall survival (OS) was 9.0 versus 8.7 months, response rate 31.8% versus 25.8%, time to treatment failure (TTF) 4.0 versus 3.4 months for IF and CF, respectively. The difference in TTF was statistically significant (P = 0.018). IF was better in terms of toxic deaths (0.6% versus 3%), discontinuation for toxicity (10.0% versus 21.5%), severe neutropenia, thrombocytopenia and stomatitis, but not diarrhea.. IF did not yield a significant TTP or OS superiority over CF, and the results of noninferiority of IF were borderline. However, IF may provide a viable, platinum-free front-line treatment alternative for metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Quality of Life; Stomach Neoplasms

To evaluate the efficacy and toxicity of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FOLFOX-6) combination therapy in patients with advanced or recurrent gastric cancer.. Patients with previously untreated advanced or recurrent gastric cancer received oxaliplatin 100 mg/m(2) and leucovorin 400 mg/m(2) (2-hour intravenous infusion) followed by a 5-FU bolus of 400 mg/m(2) (10-min infusion) and then 5-FU 2,600-3,000 mg/m(2) (46-hour continuous infusion). The chemotherapy was repeated every 14 days.. Fifty-one patients were enrolled in this study. Of these, 46 were assessable for efficacy, and all patients were assessable for toxicity. Three of 51 patients achieved a complete response, and 18 had partial responses, giving an overall response rate of 41.2%. Stable disease was observed in 11 (21.6%) patients and progressive disease in 14 (27.5%). The median time to progression was 5.4 months, and the median overall survival was 12.1 months. NCI-CTC grade 3/4 hematological toxicities were neutropenia and anemia in 9.8 and 7.8% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in 3 (5.9%) patients. Other NCI-CTC grade 3 or 4 toxicities included diarrhea in 3 patients (5.9%) and vomiting in 5 (9.8%). There were no treatment-related deaths.. This oxaliplatin/5-FU/folinic acid regimen shows good efficacy and an acceptable toxicity profile in advanced or recurrent gastric cancer patients; further clinical trials are warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pilot Projects; Recurrence; Stomach Neoplasms; Survival Rate

To determine the dose-limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced gastric cancer (GC).. Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a 1-h intravenous (i.v.) infusion followed by 5-FU as a bolus i.v. infusion on Days 1, 8 and 15. A 2-h i.v. infusion of l-leucovorin was started at the same time as the paclitaxel infusion on Days 1, 8 and 15. Treatment cycles were repeated every 28 days until disease progression or unacceptable toxicity occurred. Patients were scheduled to receive 5-FU, l-leucovorin and paclitaxel at four dose levels (mg/m(2)/week): 500/250/60 (level 1), 500/250/80 (level 2), 600/250/80 (level 3) and 600/250/100 (level 4), respectively.. Eighteen patients were enrolled. During the first cycle of the highest dose level (level 4), two of the six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash. Furthermore, three of the four patients who received the second consecutive cycle of treatment at dose level 4 had Grade 4 neutropenia. Dose level 3 was thus determined to be the MTD. Eleven (61%) of the 18 patients had partial responses, and the median progression-free survival time was 6.8 months.. The MTD and the recommended dose for phase II studies of this regimen were determined to be 5-FU 600 mg/m(2)/week, l-leucovorin 250 mg/m(2)/week and paclitaxel 80 mg/m(2)/week.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Stomach Neoplasms

The combination of docetaxel (Taxotere), cisplatin, and fluorouracil improved efficacy in gastric cancer, but was associated with substantial toxicity. This study was designed to incorporate docetaxel into a tolerable biweekly (once every 2 weeks) oxaliplatin-based chemotherapy regimen.. Patients with measurable, metastatic adenocarcinoma of the stomach or esophagogastric junction and no prior chemotherapy received oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 2600 mg/m(2) as a 24-h infusion in combination with docetaxel 50 mg/m(2) (FLOT) on day 1 every 2 weeks. Prophylactic growth factors were not administered.. Fifty-nine patients were enrolled; 54 received treatment. Patients had a median age of 60 years (range 29-76) and most (93%) of them had metastatic disease. Objective responses were observed in 57.7% of patients with a median time to treatment response of 1.54 months. Median progression-free survival (PFS) and overall survival were 5.2 and 11.1 months, respectively. Twenty-five percent of patients experienced prolonged (>12 months) PFS. Frequent (>10%) grade 3 or 4 toxic effects included neutropenia in 26 (48.1%), leukopenia in 15 (27.8%), diarrhea in 8 (14.8%), and fatigue in 6 (11.1%) patients. Complicated neutropenia was observed in two (3.8%) patients, only.. Biweekly FLOT is active and has a favorable safety profile.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Taxoids

We analysed the efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) chemotherapy as second-line treatment for metastatic or relapsed gastric cancer (MRGC) in a clinical practice setting. Factors to select patients who may benefit from salvage chemotherapy was also analysed.. Patients with MRGC with progression on or within 6 months after discontinuing platinum-based chemotherapy received FOLFIRI as second-line therapy. The FOLFIRI regimen consisted of irinotecan (180 mg/m(2); day 1) combined with leucovorin (200 mg/m(2)), followed by 5-fluorouracil (400 mg/m(2)) as a bolus and 600 mg/m(2) as a 22-h infusion on days 1 and 2 every 2 weeks.. Fifty-one patients received a total of 282 courses of chemotherapy. No patients had complete remission (CR), but 9 patients achieved partial remission (PR). Stable disease (SD) was documented in 15 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.2 and 9.1 months, respectively. Toxicities were tolerable and grade 3/4 neutropenia was observed in 49 cycles (17%). In multivariate analysis, patients with less organ involvement by metastasis and good performance status (PS) were independently associated with a longer PFS and OS (P < 0.05). Disease control (CR, PR or SD) after first-line chemotherapy were related to a longer PFS (P = 0.02), but had no effect on OS.. FOLFIRI was tolerable and showed modest activity as a second-line therapy in MRGC. Less organ involvement by metastasis or good PS may be optimal selection criteria for patients with MRGC who are suitable for second-line chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Multivariate Analysis; Patient Selection; Proportional Hazards Models; Salvage Therapy; Stomach Neoplasms; Survival Analysis

To evaluate the efficacy and toxicity of a biweekly DOF regimen consisting of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer.. The biweekly DOF regimen was administered in 37 advanced gastric cancer patients. Docetaxel, oxaliplatin and leucovorin were given intravenously at a dose of 35 mg/m2, 85 mg/m2 and 200 mg/m2 for 1 h, 2 h and 2 h on D1, respectively, and 5-Fu was administered as continuous intravenous infusion for 48 h at a dose of 1500 mg/m2 on D1 and D2. This regimen was repeated every 2 weeks. The efficacy and toxicity were evaluated after completion of 3 cycles at least.. The overall response rate (RR) of this series was 67.6%, complete response rate and partial response rate were 27.0% and 40.5%, respectively. The time to progression (TTP) was 9.2 months, and median survival time (MST) was 13.7 months. The RRs of 11 chemotherpy-naïve patients and 26 patients pre-treated with chemotherapy were 81.8% and 61.5%, respectively.. Our preliminary results showed that this biweekly combination regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin is effective and tolerable for advanced gastric cancer. However, further investigation of this regimen is mandatory.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Taxoids; Vomiting; Young Adult

To evaluate the efficacy of r oxaliplatin plus 5-fluorouracil/leucovorin calcium (LV) combined with concurrent radiotherapy in the treatment of local advanced gastric cancer.. 83 patients with local advanced gastric cancer were randomized into 2 groups. Group I (n = 40) underwent irradiation at the dose of 40 - 45 Gy 5 times a week on the primary tumor and the lymph nodes with the size > or = 10 mm in short axis, and receiving intravenous drip of OXA 85 mg/m2 for 2 h, intravenous injection of LV 200 mg/m2, and then intravenous injection of 5-fu 300 mg/m2, followed by continuous intravenous infusion of 5-fu 500 mg/m2, for 22 h, with 2 weeks as a cycle. Three cycles of chemotherapy were given during the radiotherapy. Then operative evaluation was conducted. Those resectable underwent operation and then 3 cycles of adjuvant chemotherapy. Those un-resectable underwent continuous 3 cycles of chemotherapy. Group II (n = 43) received only chemotherapy. The treatment was repeated until disease progression or prohibitive toxicity.. 38 patients were evaluated in Group I, the result showed complete remission (CR) in 4 patients (10.5%), partial remission (PR) in 23(60.5%), no-change (NC) in 7(18.4%), progressive disease (PD) in 5(13.2%), with the remission rate (RR) of 71% (27/40). 42 patients were evaluated in Group II, the result showed CR in 3 patients (7.14%), PR in 16(14.3%), NC in 13(30.9%), and PD in 9(26.2%)with the RR of 45% (19/43). The resection rates of Groups I and II were 32.5% and 27.9% respectively (P = 0.649). The R0 resection rates of Groups I and II were 77.8% and 57.1% respectively (P = 0.161). The mean survival times of the resectable patients in Groups I and II were 45 months and 28 months respectively, and the 2-year overall survival (OS) of the resectable patients in Groups I and II were 65.8% and 56.3% respectively (P = 0.371). The mean survival times of the un-resectable patients in Groups I and II were 14 months and 9 months respectively, and the 2-year OS rates of the un-resectable patients in Groups I and II were 28.3% and 20.7% respectively (P = 0.017). The toxic and adverse effects included gastrointestinal and hematological toxicity. There was no treatment-related death.. Radiotherapy combined with concurrent chemotherapy may be an effective and well-tolerated regimen in patients with advanced and metastatic gastric cancer.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms

The objective of this study was to evaluate the efficacy and safety of the POF regimen (biweekly 5-fluorouracil/leucovorin combined with paclitaxel and oxaliplatin) as first-line treatment for advanced gastric cancer (AGC). Twenty-seven previously untreated patients with advanced adenocarcinoma of the gastric or gastroesophageal junction were eligible for this study. The chemotherapy regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of 5-fluorouracil (2400 mg/m(2)) over a 46-hour period. Twenty-one patients had measurable lesions: four complete responses, eight partial responses and seven stable diseases. At a median follow-up of 610 days, median survival was 348 days. Frequent grade 3 to 4 toxicities were: neutropenia (29.6%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), and fatigue (18.5%). No treatment-related deaths occurred. The POF regimen appears to be efficacious and is well tolerated in patients with AGC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Stomach Neoplasms; Treatment Outcome

The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy.. Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion.. The percentage of patients presenting with grade >/=2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001).. This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

Topics: Acute Disease; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Stomach Neoplasms

The aim of this study was to investigate the efficacy and safety of the combination chemotherapy of paclitaxel, infusional 5-fluorouracil (5-FU) and leucovorin (FLT regimen) in advanced gastric cancer. The primary end point was the time to progression (TTP).. Patients with evaluable disease with or without measurable lesions received 175 mg/m2 paclitaxel on day 1 followed by 20 mg/m2 leucovorin and 24-h infusion of 5-FU 1,000 mg/m2 (day 1-3) repeated every 3 weeks.. Sixty patients were enrolled. The median TTP and overall survival duration were 13 and 60 weeks, respectively. One-year survival rate was 53.3%. Of the 50 patients with measurable lesion, the overall response rate was 31.7%. The most common grade 3-4 adverse event was neutropenia (61.7%).. The FLT regimen showed an efficacy comparable to other regimens of cisplatin or anthracycline combinations with the advantage of remarkably low non-hematological toxicity. These data about the efficacy of this regimen need confirmation in a phase III trial.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Analysis

Irinotecan, in combination with 5-fluorouracil (5-FU) or cisplatin, has demonstrated efficacy against advanced gastric cancer (AGC).. Chemotherapy-naive AGC patients were randomly assigned to receive irinotecan 150 mg/m(2) on day 1, leucovorin 20 mg/m(2) and a 22-h infusion of 5-FU 1000 mg/m(2) on days 1 and 2 (ILF) or ILF plus cisplatin 30 mg/m(2) on day 2 (PILF). Treatment was repeated every 2 weeks.. Of 91 registered patients, 45 patients were treated with ILF and 45 with PILF. For both arms, 687 chemotherapy cycles were delivered (median = 7 for ILF and 8 for PILF). Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms. Four patients died during treatment: one in the ILF and three in the PILF arm. The objective response rate was 42% for both arms. There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival (4.8 versus 6.2 months; P = 0.523) and overall survival (10.7 versus 10.5 months; P = 0.850).. Both ILF and PILF are active as first-line chemotherapy for AGC. The addition of cisplatin, however, has no clear advantage over ILF.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Quality of Life; Stomach Neoplasms; Surveys and Questionnaires; Treatment Outcome

This phase II study describes the efficacy and safety of combination chemotherapy of 5-fluorouracil (5-FU), low-dose leucovorin, and oxaliplatin (FLOX regimen) for pretreated advanced gastric cancer.. Patients who had been previously treated with greater than or equal to one regimen were enrolled. Patients received an oxaliplatin 75 mg/m(2) on day 1, 5-FU 1000 mg/m(2) on days 1-3, and leucovorin 20 mg/m(2) on days 1-3, every 3 weeks. The primary end point was overall survival (OS).. Among the 52 patients enrolled, 26 patients were treated as second line, and the remaining 26 patients were enrolled as third- or fourth line. A total of 203 cycles of chemotherapy were administered with the median being three cycles (range 1-15) per patient. The median OS was 6.6 months [95% confidence interval (CI) 4.5-8.8] and the median progression-free survival was 2.5 months (95% CI 1.9-3.0). The response rate was 4% (95% CI 0-9%), and the disease control rate was 48% (95% CI 34-62%). The most common toxic effects of grade 3/4 were neutropenia (16%) and vomiting (6%).. The FLOX regimen showed modest activity as a salvage treatment in pretreated advanced gastric cancer with a favorable compliance.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Stomach Neoplasms

Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.. Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and 5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided.. From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26).. Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cisplatin; Diarrhea; Disease-Free Survival; Epirubicin; Female; Fluorouracil; Gastrectomy; Hematologic Diseases; Humans; Immunohistochemistry; Italy; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Mucositis; Neoplasm Staging; Patient Compliance; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Treatment Outcome; Vomiting

This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer.. Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2), and oxaliplatin 85 mg/m(2) (FLO) every 2 weeks or fluorouracil 2,000 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2) weekly, and cisplatin 50 mg/m(2) every 2 weeks (FLP). The primary end point was progression-free survival (PFS).. Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively.. FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Germany; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Treatment Outcome

The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.. Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.. The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032).. Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.

Topics: 3' Untranslated Regions; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Disease-Free Survival; DNA, Neoplasm; Female; Fluorouracil; Genotype; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Polymorphism, Genetic; Prospective Studies; Stomach Neoplasms; Thymidylate Synthase

This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients.. Patients with histologically proven, metastatic gastric adenocarcinoma, aged 18-70 years, performance status zero to two, no prior chemotherapy, and with signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day 1, and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, which was repeated every 2 weeks.. From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24-69). In total, 386 cycles were administered with a median of nine cycles per patient (range 1-12 cycles) and 45 of 48 patients were assessable for treatment response. An independent review of tumor responses resulted in overall response rate of 66.7% (95% confidence interval=53.4% to 80.0%) by intent-to-treat analysis with one complete response and 31 partial responses. The median survival of all patients was 14.8 months and the median time to progression was 9.6 months. Most common grade 3/4 toxic effects were neutropenia (12% of all cycles) and emesis (8% of all cycles). Grade 2 peripheral neuropathy occurred in five patients. One (2%) patient had severe tumor bleeding and five (10%) patients experienced grade 3 diarrhea.. The modified FOLFOXIRI combination chemotherapy showed a very promising preliminary antitumor activity and was generally well tolerated as a first-line treatment of patients with metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Signet Ring Cell; Disease Progression; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Stomach Neoplasms; Survival Rate; Time Factors; Treatment Outcome

The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.. Untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg/m(2) intravenously (i.v.) followed by weekly doses of 250 mg/m(2), CPT 11 180 mg/m(2) i.v. on day 1, LFA 100 mg/m(2) i.v. followed by 5-FU 400 mg/m(2) i.v. bolus, and 600 mg/m(2) i.v. 22-h continuous infusion on days 1 and 2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in patients with a complete response, partial response, or stable disease. Antitumor activity was assessed by computed tomography (CT) and positron emission tomography (PET) at baseline and after 6 weeks, and further by CT alone or CT and PET every 6 weeks.. Thirty-eight patients were enrolled (median age 63.5 years, range 39-83; median Karnofsky performance status 90, range 70-100; stomach 89.5% and GEJ 10.5%; locally advanced disease 13.2% and metastatic disease 86.8%). All 38 patients were assessed for safety and survival, and 34 patients were assessed for overall response rates (ORR). The ORR was 44.1% [95% confidence interval (CI) 27.5% to 60.9%]. The median time-to-progression was 8 months (95% CI 7-9). At the median follow-up time of 11 months, 55.3% of patients were alive, with a median expected survival time of 16 months (95% CI 9-23). Grade 3-4 toxicity included neutropenia (42.1%), acne-like rash (21.1%), diarrhea (7.9%), asthenia (5.3%), stomatitis (5.3%), and hypertransaminasemia (5.3%). There was one (2.6%) treatment-related death.. The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Italy; Kaplan-Meier Estimate; Karnofsky Performance Status; Leucovorin; Male; Middle Aged; Positron-Emission Tomography; Stomach Neoplasms; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

To analyze the results of postoperative concomitant radiochemotherapy with 5-florouracil (5-FU) and leucovorin (LV) in patients with gastric carcinoma treated in a single institution.. During 2001-2004, 123 patients with the mean age of 60 years, were treated for adenocarcinoma of the stomach, stage Ib-IV, with postoperative concomitant radiochemotherapy. Radical (R0) and non-radical (R1) resection of the tumor was performed in 107 and 16 patients, respectively. Adjuvant treatment consisted of five cycles of five-day chemotherapy with 5-FU (425 mg/m(2)) and LV (20 mg/m(2)) and concomitant radiotherapy with the total dose of 45 Gy.. The treatment was completed according to the protocol in 101 patients. Stomatitis, dysphagia, and nausea and vomiting of grade three occurred in 32, 27, and 23 patients, respectively. The median follow-up time of 87 survivors was 30.4 months (range 17.4-58.3 months). At two years, locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates were 86%, 65%, 74%, and 73%, respectively. In the multivariate analysis, the initial Hb level was identified as independent prognostic factor for all survival four endpoints, the involvement of whole stomach with cancer for LRC, the total dose of 5-FU per five-day cycle for DFS, and pT stage for DSS.. In operable gastric carcinoma, postoperative concomitant radiochemotherapy with 5-FU and LV is feasible and its toxicity acceptable. Its potential to improve the treatment outcome compared to the surgery alone is yet to be tested in well designed prospective randomized studies.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Radiation Dosage; Radiotherapy, Adjuvant; Risk Factors; Slovenia; Stomach Neoplasms; Treatment Outcome

This study aimed at evaluating the feasibility and toxicity of a salvage therapy with mitomycin C (MMC), 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with cisplatin-resistant advanced gastric cancer.. A 3-patient cohort dose-escalating study design was used. The patients received FLO: oxaliplatin 85 mg/m2, 5-FU 2,600 mg/m2 (24 h), leucovorin 200 mg/m2 on days 1, 15, and 29 plus MMC on day 1 (FLOM). The MMC dose was escalated from 6 to 12 mg/m2 in 2- mg/m2 steps. Cycles were repeated every 6 weeks.. Twenty patients were enrolled in 4 treatment cohorts. The treatment was well tolerated with grade 3 or 4 nonhematological toxicities affecting less than 5% of patients. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia were observed in 9 (45%), 7 (35%), and 5 (25%) of 20 patients, respectively. Mild but prolonged thrombocytopenia was dose limiting, requiring treatment discontinuation or a treatment delay >or=2 weeks in 8 (40%) of 20 patients. MMC 10 mg/m2 every 6 weeks was considered as the optimal dose in combination with FLO. Objective responses were observed in 7 (35%) of 20 patients, and 7 further patients (35%) had stable disease. Median time to progression and overall survival were 4.1 and 8 months, respectively.. Prolonged cumulative myelotoxicity was dose limiting in the therapy with MMC, 5-FU, and oxaliplatin. This combination chemotherapy seems to overcome cisplatin resistance in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Feasibility Studies; Female; Fluorouracil; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Stomach Neoplasms; Terminal Care; Treatment Outcome

Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients.. From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided.. The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm.. Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Stomach Neoplasms; Survival Analysis

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur-uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided doses on days 1-22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24-52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5-7.5 months); overall survival was 9.5 months (95% CI 8.5-13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Epirubicin; Female; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome; Uracil

To determine the activity and toxicities of a low dose leucovorin (ldLV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric cancer. Patients were treated with cycles of oxaliplatin 85 mg/m2 on day 1 plus LV 20 mg/m2, followed by 5-FU a 400 mg/m2 bolus and a 22 hour continuous infusion of 600 mg/m2 5-FU on days 1 - 2 every two week intervals. Forty-five patients were enrolled in this study. Forty-two patients were assessable for response. One of the 42 patients demonstrated complete response, and 20 partial responses, and overall response rate of 50%. The median time to progression and overall survival time were 7.7 months (95% CI: 3.6 - 11.9 months) and 11.2 months (95% CI: 9.1 - 13.3 months), respectively. Major hematologic toxicities included grade 1 - 2 anemia (39.7%), neutropenia (30.4%) and grade 3 - 4 neutropenia (10.9%). Twelve cycles were associated with neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%). There was no treatment related death. The modified FOLFOX-4 regimen was found to be a safe and effective first line therapy in advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Korea; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Stomach Neoplasms; Survival Analysis; Time Factors; Treatment Outcome

To assess the toxicity and activity of bolus mitomycin C (MMC) in combination with a 24-hour continuous infusion of 5-fluorouracil (5-FU) in gastric cancer patients who had received at least one prior chemotherapy regimen.. Patients were treated with MMC (10 mg/m(2)) on days 1 and 22, 5-FU (2.6 g/m(2)) as a 24-hour infusion, and folinic acid 500 mg/m(2) weekly for 6 weeks.. Thirty-four patients with gastric cancer, 16 after failure of first-line chemotherapy and 18 after failure of at least two prior chemotherapies, were included. In the intent-to-treat analysis, 9 (26.5%) of the 34 patients had a partial response and 10 (29.4%) a disease stabilization (disease control rate 56%). The median time to progression was 3.3 months (CI95: 2.8-3.7), and the median overall survival was 7.2 months (CI95: 5.9-8.4). Grade III/IV thrombocytopenia occurred in 14.7% of patients (n = 5), while the most frequent nonhematological grade III/IV toxicities were mucositis and diarrhea, each affecting 9% of patients.. As the tested regimen was generally safe and well tolerated by the patients, MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen for patients with advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Staging; Retreatment; Stomach Neoplasms; Survival Rate

This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients.. From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy.. A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal.. In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Stomach Neoplasms

This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials.. A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate.. Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively.. Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Europe; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Prospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F).. Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m(2) and P 50 mg/m(2) on days 1, 15 and 29 and L 500 mg/m(2) plus F 2000 mg/m(2) weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m(2), P 40 mg/m(2), L 200 mg/m(2) and F 2000 mg/m(2). The primary endpoint was response rate.. Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease).. T-PLF regimen is highly active and has a favorable toxicity profile.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Docetaxel; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Taxoids

Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function.. Between December 2000 and September 2003, 27 patients were treated at Tübingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m2), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m2/24 h). A dose constraint of

Topics: Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Chemotherapy, Adjuvant; Cisplatin; Creatinine; Esophagogastric Junction; Female; Fluorouracil; Humans; Kidney; Leucovorin; Male; Middle Aged; Paclitaxel; Radiotherapy Dosage; Radiotherapy, Adjuvant; Stomach Neoplasms

To investigate the effects of Shenqi Fuzheng injection (SQFZI) combined with docetaxcl, flurouracil and calcium folinate in treating advanced gastric carcinoma, and to evaluate the action of SQFZI for enhancing therapeutic effect and alleviating adverse reaction of chemotherapy.. Sixty advanced gastric cancer patients were assigned to two groups randomly, the control group treated with chemotherapy alone and the treated group treated with SQFZI combined chemotherapy. Chemotherapy regimens (TFC) was given to all patients consisting of docetaxel 75 mg/m2 intravenous dripping on the 1st day, flurouracil (5-FU) 350 mg/m2 and calcium folinate (CF) 120 mg/m2 intravenous dripping with micro-pump continuously from day 1 to 5, for 21-28 days as a cycle. To patients in the treated group, starting from 3 days before chemotherapy, SQFZI 250 mL was dripped every day for 14 successive days. The clinic effects were evaluated after two-cycle treatment.. The short-term effective rate was 40.0% in the treated group and 33.3% in the control group. As compared with those in the control group, patients in the treated group after treatment had a higher Karnofsky score (chi2 = 7.21, P < 0.05) and body weight (chi2 = 11.47, P < 0.05), lesser adverse reactions in decreasing of peripheral blood leucocyte, damage of peripheral nerve, adverse reaction of gastrointestinal tract, as well as better immune function.. SQFZI could effectively improve the clinical symptoms induced by chemotherapy regimen TFC, alleviate the adverse reaction, raise patients' quality of life and their immune function.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Fluorouracil; Humans; Injections; Leucovorin; Male; Middle Aged; Phytotherapy; Stomach Neoplasms; Taxoids; Treatment Outcome

This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer.. Patients were treated with irinotecan 150 mg/m(2) on day 1 and received ldLV 20 mg/m(2) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22 h continuous infusion) on days 1 and 2 every 14 days.. A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31-70), and 55.6% (20/36) of the patients had performance status (ECOG) of 0 or 1. The median follow-up duration was 15.5 (range 2.6-36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% CI 0.0-21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 (95% CI 2.0-4.6) months, and the median overall survival time was 10.9 (95% CI 6.1-15.7) months. The median number of cycles of modified FOLFIRI treatment was 3 (range 1-9 cycles). Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade III nausea/vomiting was found in one patient (2.8%). There was one episode of UGI bleeding, but there were no treatment-related deaths.. The modified FOLFIRI regimen described here appears a safe and feasible salvage therapy in advanced gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Follow-Up Studies; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Nausea; Salvage Therapy; Stomach Neoplasms; Stomatitis; Survival Rate; Treatment Outcome

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m(2)) and cisplatin (60 mg/m(2)) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Paclitaxel; Stomach Neoplasms; Survival Rate; Treatment Failure

To assess the therapeutic efficacy and adverse effects of endogenetic field hyperthermia (EFH) in combination with L-OHP /LV / 5-FU in the treatment of advanced gastric cancer.. This study included 147 surgical patients with stage II-IV gastric cancer, who received postoperative chemotherapy with FOLFOX (L-OHP 85 mg /m square, 3 h intravenous infusion, followed by infusion of LV at 200 mg /m square in 2 h, intravenous injection of 5-Fu at 400 mg /m square, and intravenous infusion of 5-FU at 3000 mg /m square in 48 h). Eight treatment cycles (each lasting for 14 days) were administered. In 68 cases randomly selected from the cohort, EFH was performed on the first and third days (treatment group), but not in the other 79 cases (control group).. The response rate was 68.4% in the treatment group and 36.4% in the control group, showing significant difference between them (P<0.05). The 1-year survival rate was 88.2% in the treatment group, similar to the rate of 81.0% in the control group (P< 0.05), but the 3, 5-year survival rates in treatment group (67.6% and 30.9%) was significantly higher than those in the control group (47.6% and 15.4%, P<0.05). The adverse effects were similar between the two groups.. EFH combined with the chemotherapeutic regimen FOLFOX might improve the therapeutic effect of stage II-IV gastric cancer without obviously increasing the adverse effects.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Stomach Neoplasms; Treatment Outcome

To investigate the therapeutic value and safety of the biweekly regimen of 5-fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F 35/15; median age = 65) with AGC, none of whom had received chemotherapy for advanced disease, were accrued in this trial. Fifteen patients (30%) were 70 years old or older. At the time of their accrual, cytotoxic chemotherapy, consisting of LV 100 mg/m(2) (2-hour i.v. infusion) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22-hour continuous infusion) on therapeutic days 1 and 2 plus CPT-11 180 mg/m(2) (1-hour infusion) on day 1, was initiated. Treatment courses were repeated every 2 weeks until evidence of progressive disease, unacceptable toxicity or withdrawal of consent. All patients were assessable for toxicity and 48 of 50 for response evaluation, having completed at least four courses of chemotherapy. Complete response was achieved in 2 patients (4%, intent to treat) and partial response in 16 (32%) (overall response rate, 36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had stable disease and 6 patients (16%) progressed. The median time to progression was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI: 6-22 months). Between the subgroups of patients <70 years old and 70 or older, there were no significant differences in efficacy. One toxic death occurred. Treatment tolerance was generally mild to moderate and easy to treat. The main grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%). Grade 3-4 neutropenia was the only treatment-related serious adverse event significantly more common in patients older than those aged <70 (53.3% vs 22.8%, respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5-FU plus CPT-11 in untreated patients with AGC is active and has an acceptable safety profile. Further evaluation of this regimen seems to be warranted in a phase III trial.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Treatment Outcome

Cisplatin (DDP) in large dosage impairs renal functions, while the impact of fractionated low dose DDP on renal functions is unclear. This study was to evaluate the effects of fractionated low dose DDP on renal functions of gastric cancer patients.. From Sep. 1998 to Jun. 2002, 31 gastric cancer patients were treated with LFEP regimen at School of Oncology of Peking University: intravenous administration of calcium folinate (CF, 150 mg/m(2)) at Day 1-3, 5-fluorouracil (5-FU, 500 mg/m(2)) at Day 1-5, epirubicin (EPI, 60 mg/m(2)) at Day 1, and DDP (20 mg/m(2)) at Day 1-3. Urine N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transferase (gamma-GT) and routine urine test were assessed before chemotherapy and every other day during the 14-day chemotherapy; serum creatinine (sCr) and urea nitrogen (BUN) were assessed at the 7th day and 14th day during treatment.. Of the 31 patients, 13 had normal renal functions before chemotherapy, while only 1 had normal renal functions after chemotherapy. Urine NAG and gamma-GT were changed significantly after chemotherapy: they were increased significantly on the 4th day and maintained higher than normal level for another 14 days thereafter. Meanwhile, no significant change in sCr and BUN were observed.. Combined chemotherapy with fractionated low dose DDP still adversely affects renal functions of gastric cancer patients, however, the long-term effects need to be clarified.

Topics: Acetylglucosaminidase; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Urea Nitrogen; Cisplatin; Creatinine; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; gamma-Glutamyltransferase; Humans; Kidney Function Tests; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Clinical studies regarding chemotherapy for gastric cancer patients with malignant ascites have been classically rather limited in scope, largely because peritoneal seeding produces no measurable lesions, and patients generally exhibited poor performance status. Herein, we have evaluated the efficacy and toxicity of a fortnightly modified FOLFOX-4 (m-FOLFOX) regimen.. Gastric cancer patients with cytologically confirmed malignant ascites were treated with cycles of oxaliplatin at 85 mg/m(2) plus leucovorin 20 mg/m(2) on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 400 mg/m(2) bolus and a 22 h continuous infusion of 600 mg/m(2) 5-FU on Days 1-2 at 2-week intervals.. Forty-eight patients participated in this study. Twenty-two patients (45.8%) were treated with m-FOLFOX-4 as a first line palliative treatment. Twenty-one patients (43.8%) were adjudged to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Thirty-six patients were assessable and exhibited measurable lesions. Twelve (33.3%) patients evidenced partial responses. Decreases or disappearances of ascites levels were observed in 17 (35.4%) patients. The median time to progression and overall survival time were 3.5 (95% CI: 2.9-4.1) months and 8.4 (95% CI: 4.9-11.9) months, respectively. Major hematologic toxicities included Grades 1-2 anemia (53.9%), neutropenia (41.6%) and, Grades 3-4 neutropenia (15.8%). The most frequently detected non-hematological toxicities were Grades 2 and 3 nausea/vomiting (17%). We noted no deaths related to treatment.. The m-FOLFOX-4 regimen utilized herein was determined to be both safe and feasible even for gastric cancer patients with malignant ascites in poor performance status.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma; Disease-Free Survival; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Vomiting

The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU)/leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Treatment consisted of irinotecan 80 mg/m(2) intravenously (i.v.), followed by LV 200 mg/m(2) (i.v.) and 5-FU 450 mg/m(2) as an i.v. bolus, administered weekly for 6 weeks, followed by a 2-week rest period. Thirty-one patients (23 chemo-naïve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 3 toxicity was febrile neutropenia. Grade 3 non-hematological toxicities were rare. There were no treatment-related deaths. The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation would be worthwhile, particularly in elderly or debilitated patients who cannot tolerate aggressive chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Stomach Neoplasms

It has been demonstrated that the 3-weekly PELF regimen is superior to FAM and FAMTX in advanced gastric cancer. The aim of this multicentric phase II study was to evaluate the efficacy and tolerability of a PELF regimen, given every 2 weeks as a first-line therapy in patients with unresectable or metastatic gastric carcinoma.. Fifty-nine patients were treated with the following schedule: cisplatin (40 mg/m2, day 1), epirubicin (30 mg/m2, day 1), 5-fluorouracil (400 mg/m2 bolus, followed by 600 mg/m2, 22 h continuous infusion, day 1 and 2) and folinic acid (100 mg/m2, 2-h infusion, day 1 and 2). G-CSF (5 microg/kg) was administered on day 6, 8, 10, and 12. Cycles were repeated every 2 weeks for a maximum of twelve courses.. Of the 52 evaluable patients, three (5.8%) complete responses, and 15 (28.8%) partial responses were observed, for an overall response rate of 34.6%. The median duration of response was 8 months. Nineteen patients had stable disease and 15 progressed on therapy. At a median follow-up of 12 months, the median time to progression was 8 months and the median survival duration was 13 months, with a 1-year survival rate of 53.5%. Grade 3 or 4 observed toxicities were: neutropenia in 26 patients (44%), thrombocytopenia in four patients (6.7%), and mucositis in seven patients (11.9%).. The bi-weekly PELF regimen seems to be feasible with an acceptable toxicity profile and an activity comparable to the 3-weekly schedule.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Recombinant Proteins; Stomach Neoplasms; Time Factors

The standard chemotherapy regimen for advanced gastric cancer has not yet been established. We investigated the efficacy and the safety of the combination of docetaxel with infusional 5-fluorouracil (5-FU) and leucovorin (FLT) in advanced gastric cancer.. Patients received docetaxel 75 mg/m(2) (1-hour infusion) followed by a leucovorin bolus 20 mg/m(2) and a 24-hour infusion of 5-FU 1,000 mg/m(2) (day 1-3) every 3 weeks. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the toxicity was evaluated by National Cancer Institute common toxicity criteria (NCI-CTC).. Sixty-six patients were enrolled. Median relative dose intensity was 86%. Of 57 evaluable patients, the overall response rate was 25.7%. The response rate was 34.2% in chemonaïve patients and 14.2% in the patients who had previously received treatment. Median time to progression and overall survival duration were 5.2 and 9.7 months, respectively. The most frequent grade 3-4 toxicity was neutropenia, which was the major cause of treatment delay. Other hematological and nonhematological toxicities were rare.. The FLT regimen showed a comparable efficacy with other second-generation regimens. Because of the low nonhematological toxicity, this could be a potential alternative to the cisplatin-containing regimens in gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Docetaxel; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Taxoids; Treatment Outcome

As no standard chemotherapy regimen has been established for advanced gastric cancer, this study sought to evaluate the efficacy and safety of combination chemotherapy that included paclitaxel and leucovorin (LV)-modulated infusional 5-fluorouracil (5-FU) in metastatic gastric cancer. Patients received a three-hour infusion of 175 mg/m2 of paclitaxel on day 1. A bolus of 20 mg/m2 of LV was then administered, followed by a 24-h infusion of 1,000 mg/m2 of 5-FU on days 1 through 3. The treatment cycle was re-peated every 3 weeks until disease progression. Response evaluation was performed according to the RECIST criteria, with toxicity determined by NCI-CTC (version 2.0). A total of 66 patients, including 21 (31.8%) with a history of prior chemotherapy, were enrolled. Fifteen (71.4%) of the 21 patients with prior chemotherapy received prolonged infusional 5-FU. In the 56 evaluable patients (37 in the chemotherapy-naïve group and 19 in the prior chemotherapy group), tumor responses according to prior exposure to chemotherapy were as follows: 17 (45.9%) partial response (PR), 6 (16.2%) stable disease (SD) and 14 (37.8%) progressive disease (PD) in the chemotherapy-naïve group; 1 (7.1%) complete response, 3 (15.8%) PRs, 8 (42.1%) SDs and 7 (36.8%) PDs in the prior chemotherapy group. The overall median response duration was 20 weeks (range, 8-61 weeks), with a median progression-free survival of 20 weeks [95% confidence interval (CI), 13.4-26.6 weeks] and 12 weeks (95% CI, 5.7-18.3 weeks) in the chemotherapy-naïve and prior chemotherapy groups, respectively. The median overall survival was 48 weeks (95% CI, 38-58 weeks) in the chemotherapy-naïve group and 28 weeks (95% CI, 22-34 weeks) in the prior chemotherapy group. The most frequent grade III/IV toxicity was neutro-penia. Non-hematological toxicity of grade III/IV was rare. Paclitaxel in combination with 5-FU/LV is clinically beneficial for patients with advanced gastric cancer and is a feasible salvage regimen for 5-FU-refractory gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Disease Progression; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mucositis; Multivariate Analysis; Neutropenia; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Analysis; Treatment Outcome

We assessed the efficacy and safety profile of a docetaxel (Taxotere; Sanofi-Aventis, France), fluorouracil (FU), and leucovorin (LV) combination (TFL), as first-line chemotherapy in patients with advanced gastric cancer.. Fifty-eight patients with advanced gastric cancer were entered in this phase II study. The chemotherapy regimen (TFL) was administered in an outpatient setting as follows: docetaxel 7 mg/m2 on day 1 and FU 50 mg/m2 and LV 30 mg/m2 on days 1 to 3, every 3 weeks for six cycles.. On an intent-to-treat basis, 4 complete (7%) and 11 partial responses (19%) were observed, with an objective overall response rate of 26%; in addition, 22 patients (38%) had stable and 15 (26%) had progressive disease. For 6 (10%) patients, response could not be evaluated. Responses were noted at all metastatic sites. With a median follow-up of 55 months, median survival was 9 months; median time to progression, 5.9 months; and median duration of response, 10 months. Toxicity was manageable and no toxic death was reported. Neutropenia was the most frequent severe toxicity and occurred in 30% of the patients. The main non-hematologic toxicities were alopecia (76%), diarrhea (30%), and stomatitis (30%).. The results of this phase II study seem to indicate that the TFL regimen has moderate activity in patients with advanced gastric cancer, with acceptable toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Stomach Neoplasms; Survival Rate; Taxoids

Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time.. Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule.. A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%-56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 - 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 - 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 - 11.82).. OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate

The aim of the study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5-FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and leucovorin (LV) in patients with locally advanced gastric cancer.. Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2), continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days from surgery.. Thirty-eight patients were treated. Both preoperative and postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment LAP versus surgical pathological stage) was seen in 23% of patients. The R0 resection rate was 84%. Neither an increase in postoperative morbidity nor operative mortality was noted. With a median follow-up of 43.0 months, 15 patients (39.5%) are still alive (median survival 30.3 months). Good pathologic response, seen in five patients (15%), was associated with better survival (P = 0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients, respectively. Quality of life seemed to be preserved.. Neoadjuvant cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection and the survival rates are encouraging. An association between pathologic response and patient outcome was suggested.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Endoscopy, Digestive System; Feasibility Studies; Female; Floxuridine; Fluorouracil; Humans; Injections, Intraperitoneal; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Postoperative Period; Quality of Life; Stomach Neoplasms; Survival Analysis; Treatment Failure

In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy.. Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications.. Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events.. Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Anastomosis, Surgical; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Postoperative Complications; Prospective Studies; Recombinant Proteins; Stomach Neoplasms; Survival Analysis

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Paclitaxel; Prospective Studies; Safety; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.

Topics: Acetates; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Uridine

Treatment options for advanced or metastatic gastric cancer (A/MGC) are limited and inclusion of novel substances is necessary. Few studies have confirmed the activity and tolerability of the combination of oxaliplatin (OXA) and 5-fluorouracil (5-FU) modulated with leucovorin (LV) administrated to patients with A/MGC. The goal of current study was to evaluate the efficacy and toxicity of Folfox-4 regimen in patients with A/MGC.. Fifty-six patients were treated with Folfox-4 regimen. Treatment was continued until disease progression, unacceptable toxicity or until a patient chose to discontinue treatment. Responses to treatment and toxicity were recorded according to the WHO criteria and NCI toxicity criteria.. All patients were assessable for toxicity and response. Patients (71.4% male, 28.6% female) had a median age of 65 years (range, 28-78). All patients had histologically confirmed metastatic (89.3%) or advanced (10.7%) gastric cancer. Response was evaluated every 6 weeks; 1 complete (1.8%) and 23 (41.1%) partial remission were observed (overall response rate 42.9%). Twenty patients (35.7%) showed stable disease and 12 (21.4%) had a progressive disease. Median overall survival, time to progression and follow up were 10 months, 6 months, and 11.5 months, respectively. WHO grade 3 or 4 hematologic toxicities included leucopenia, neutropenia, thrombocytopenia, and anemia. No patient experienced neutropenic fever. Other grade 3/4 toxicities included nausea, vomiting, diarrhea, stomatitis, and anorexia. Three patients (5.3%) experienced grade 3 peripheral neuropathy. No treatment-related deaths were recorded.. Folfox-4 regimen is active and well tolerated in patients with advanced/metastatic gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Stomach Neoplasms

There is an argument on whether or not glutamine-supplemented parenteral nutrition is beneficial to chemotherapy in gastrointestinal neoplasm patients. The aim of this study was to prospectively evaluate the effect of parenteral nutrition with alanyl-glutamine dipeptide on gastrointestinal neoplasm patients receiving chemotherapy.. This study was a prospective, randomized double-blind clinical trial. Seventy-two patients were randomly divided into study group and control group (each group had 36 patients). The side effects during chemotherapy were observed. Serum albumin, serum pre-albumin, IgG, IgA, IgM, C3, C4 level were measured before chemotherapy and on day 4 and day 8 after chemotherapy. Nitrogen balance was also calculated simultaneously.. (1) Less side effects during chemotherapy in study group were revealed compared to those in control group (P<0.05). (2) Serum albumin and pre-albumin levels were both decreased in the two groups on day 4 after chemotherapy, and were markedly decreased in control group on day 8 after chemotherapy (P<0.05). (3) IgG, IgM, IgA levels were all decreased compared with the test results before chemotherapy on day 4 after chemotherapy in two groups, and were significantly decreased in control group on day 8 after chemotherapy (P<0.05). C3 and C4 levels were higher in study group compared with control group on day 8 after chemotherapy (P<0.05). (4) Nitrogen balance in study group was better than that in control group (P<0.05) on day 8 after chemotherapy.. Alanyl-glutamine dipeptide is beneficial to chemotherapy in gastrointestinal neoplasm patients. It could reduce the side effects of chemotherapy, which helps to improve the nutritional status, the immune function and the survival quality of patients during chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Complement C3; Complement C4; Dipeptides; Double-Blind Method; Female; Fluorouracil; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leucovorin; Male; Middle Aged; Nitrogen; Parenteral Nutrition; Prealbumin; Prospective Studies; Rectal Neoplasms; Serum Albumin; Stomach Neoplasms; Young Adult

To evaluate the efficacy and toxicity of oxaliplatin in combination with calcium folinate and fluorouracil (OXA-LV5FU2) regimen as the neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer.. Twenty-seven patients were treated with OXA-LV5FU2 before operation. Neoadjuvant chemotherapy regimens containing OXA 100 mg/m(2) iv 2 h d1, LV 200 mg/m(2) iv 2 h followed by 5-FU 400 mg/m(2) iv bolus and 5-FU 1 g/m(2) iv 48-72 h d1, 2 were administered every 2 to 3 weeks for 3 to 4 cycles before local treatment. The responses of the primary tumor and the chemotherapy toxicity were observed in each patient.. Twenty-four patients were treated with surgery. The radical resections were carried out in 14 cases. The overall clinical efficacy rate was 48.1% with 3.7% CR and 44.4% PR, SD was 33.3% and PD was 18.5%. Eight of the 27 cases were downstaged. The common toxicities were nausea, vomiting, peripheral neuropathy, leukocytopenia, alopecia and hepatosis. The toxicities relieved after symptomatic treatment. There was no relative risk of death during treatment.. OXA-LV5FU2 is a very effective and well tolerated regimen as neoadjuvant chemotherapy for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms

Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.. 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Diarrhea; Digestive System Surgical Procedures; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neutropenia; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Thrombocytopenia; Treatment Outcome

Our aim was to determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose of oxaliplatin combined with oral tegafur-uracil and leucovorin. Twenty-eight chemo-naive patients with advanced gastric cancer were enrolled. Oxaliplatin (55, 70, 85, 100 and 115 mg/m2) was given as a 2-h infusion on days 1 and 15. Oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) were given 3 times a day from days 1 to 21 (28-day cycle). DLTs were defined as grade IV hematologic toxicity or grade III non-hematologic toxicity. The MTD for oxaliplatin was 100 mg/m2. The most common DLT was diarrhea. Major grade III/IV toxicities included vomiting, diarrhea, renal dysfunction, leukopenia and thrombocytopenia. There were two treatment-related deaths. Intent-to-treat response was graded as partial response in 13 patients (46.4%; 95% confidence interval 26.74-66.12%), stable disease in nine and disease progression in five. As of June 2004, 17 patients had died. The median time to treatment failure, time to progression and overall survival were 124, 308 and 434 days, respectively. The recommended dose for the phase II study is oxaliplatin 100 mg/m2 biweekly with oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) 3 times a day for 21 days.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome; Uracil

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (5-FU) is a well-tolerated active combination therapy for advanced gastric cancer. Pegylated liposomal doxorubicin (Caelyx) has been combined with this regimen in a phase I study exhibiting promising activity in patients with upper gastrointestinal tumors. In the present study, we investigated activity and tolerability of this three-drug regimen in patients with gastric cancer. Patients with advanced or metastatic gastric cancer were recruited to receive weekly infusional 5-FU (2000 mg/m2) mixed with sodium folinic acid (FA; 500 mg/m2) in one pump (days 1, 8, 15, 22, 29, 36). On days 1 and 29, Caelyx (20 mg/m2) was given as a 1-h, and MMC (7 mg/m2) was applied as bolus injection on days 8 and 36. Treatment courses were repeated on day 57. Twenty-seven patients with a median age of 66 years were recruited in a single center; 56% had histologically proven peritoneal carcinomatosis and 26 patients are evaluable for toxicity. Common Toxicity Criteria of the National Cancer Institute grade 3 toxicity was recorded in 34% of the patients (anemia 12%, leukocytopenia 8%, febrile neutropenia 4%, thrombocytopenia 12%, nausea 15%, diarrhea 8% and mucositis 4%). One patient developed hemolytic-uremic syndrome. One complete (5%) and eight partial responses (42%) were observed in 19 patients evaluable for response according to WHO criteria. Seven patients had no change (37%) and three (16%) progressive disease. Six patients with peritoneal carcinomatosis not amenable to WHO response assessment had progression-free intervals between 8 and 21 months. Median survival for all patients was 14.7 months and median time to progression was 8.4 months. We conclude that this new three-drug combination regimen yields a promising overall response rate (47%) in patients with gastric cancer despite the inclusion of a majority of elderly patients at moderate or high risk of death in this trial. Its safety and good tolerability as established in the phase I trial was confirmed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Liposomes; Male; Maximum Tolerated Dose; Middle Aged; Mitomycin; Stomach Neoplasms; Survival Rate; Treatment Outcome

Weekly infusional 5-fluorouracil (5-FU) and folinic acid (FA) as part of multi-drug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective with low toxicity. The present analysis was carried out to evaluate the safety and efficacy of 5-FU/FA in combination with 3-weekly mitomycin C (MMC) in patients with advanced gastric cancer.. A total of 28 patients with AGC were analysed (first line n=23). They received weekly 24-h 5-FU 2,600 mg/m2 preceded by 2-h FA 500 mg/m2 for 6 weeks followed by a two week rest period. Bolus MMC 10 mg/m2 was applied on days 1 and 22. Patient characteristics were: m/f 17/11; median age 67 years (43-79). The most common metastatic sites were liver and peritoneum (n=12, respectively).. A median of 3 and a total of 91 cycles were administered. Mean dose intensity in cycle I was: 5-FU 86%, MMC 87%. Responses were observed in 43%, no change was seen in 29% of the patients. Median overall survival was 9.7 months (10.7 months for patients treated first line). Non-haematological toxicities (NCI CTC grades 3 and 4) were observed in 2 patients, leukopenia and thrombocytopenia grades 3/4 were observed in 50 and 25% of the patients, respectively.. Infusional 5-FU/FA plus MMC may safely be used in patients with AGC in the routine clinical setting. This regimen yields response rates and survival data comparable to platinum-based regimen.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Germany; Humans; Infusions, Intravenous; Leucovorin; Middle Aged; Mitomycin; Severity of Illness Index; Stomach Neoplasms; Survival Analysis; Treatment Outcome

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Stomach Neoplasms; Survival Rate

We performed a phase II study of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU) and leucovorin in metastatic gastric cancer patients who were previously treated with taxane and cisplatin, to evaluate the antitumour activity and toxicity of the combination chemotherapy. The metastatic gastric adenocarcinoma patients who were previously treated with taxane and cisplatin combination as first line, and had at least one measurable lesion, 0-2 ECOG performance status and adequate organ functions, were considered eligible. They received irinotecan (150 mg m(-2), day 1) and leucovorin (100 mg m(-2), day 1), followed by continuous infusion of 5-FU (1000 mg m(-2) day(-1), days 1 and 2) every 2 weeks. Treatment was continued until progression of disease was observed. In all, 64 patients were treated with this combination chemotherapy. The median age of the patients was 55 years (range, 33-74 years), and the median ECOG performance status was 1 (0-1, 61 (95%)). Out of 64 patients, 57 were assessable for response. Among 57 assessable patients, no complete response and 12 partial responses were observed (overall response rate, 21%; 95% confidence interval (CI), 10-32%). Stable disease was observed in 14 patients (25%) and progressive disease in 31 patients (54%). The median time to progression was 2.5 months (95% CI, 1.6-3.4) and the median overall survival since the start of the second-line modified FOLFIRI was 7.6 months (95% CI, 6.5-8.7). Grade 3-4 haematologic toxicities included neutropenia in seven patients (11%) and thrombocytopenia in five patients (8%). Grade 3-4 nonhaematologic toxicities included diarrhoea in two patients (3%) and vomiting in two patients (3%). There were no treatment-related deaths. The combination of irinotecan, 5-FU and leucovorin showed moderate activity and favourable toxicity profile as a second-line treatment in metastatic gastric cancer patients, who were previously treated with taxane and cisplatin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease Progression; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Salvage Therapy; Stomach Neoplasms; Survival Analysis; Taxoids; Treatment Outcome

The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy.. Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 h was scheduled in between the two cycles.. Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(M0) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3-25) for FLP and 18 months (2-51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% CI 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group.. Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Paclitaxel; Radiotherapy, Adjuvant; Risk Factors; Stomach Neoplasms; Survival Rate

The aim of the study was to evaluate the efficacy and tolerability of the combination of oxaliplatin, fluorouracil and leucovorin in patients with advanced esophagus cancer.. Thirty-five patients with recurrent or metastatic esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Up to one prior chemotherapy regimen was allowed. All patients had bi-dimensionally measurable disease. Patients received oxaliplatin 85 mg/m2 as a 2-h infusion on day 1. Leucovorin (500 mg/m2) followed by fluorouracil bolus (400 mg/m2) and 22-h continuous infusion fluorouracil (600 mg/m2) was administered on days 1 and 2. Granulocyte colony stimulating factor was not routinely administered unless the patient developed febrile neutropenia or prolonged neutropenia. Treatment was repeated every 14 days.. Of the thirty-five patients enrolled, all were evaluated for toxicity and 34 were evaluated for response. The overall response rate was 40% (95% confidence interval, 24% to 57%) with complete and partial response rates of 3% and 37%, respectively. The median response duration was 4.6 months, and the median overall survival was 7.1 months. One-year survival was 31%. The major toxicity noted was cumulative neutropenia, with 29% developing grade 4 toxicity. There was one treatment-related death secondary to neutropenic sepsis. The most common non-hematologic toxicity encountered with this regimen was cumulative peripheral neuropathy, with 26% experiencing grade 2 or 3 toxicity.. The combination of oxaliplatin, leucovorin, and fluorouracil shows significant anti-tumor activity and a favorable toxicity profile in patients with metastatic carcinoma of the esophagus.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophagogastric Junction; Etoposide; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Levoleucovorin; Male; Middle Aged; Neoplasm Staging; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m(-2)) plus FA (500 mg m(-2), 2-h infusion) followed by 5-FU (2000 mg m(-2), 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39-69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2-26.2 months), median survival is 11.4 months (95% CI, 8.0-14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9-9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Stomach Neoplasms; Treatment Outcome

oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer.. we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on days 1 and 2), a 5-FU (400 mg/m2) bolus injection followed by 22-h continuous infusion (800 mg/m2) on days 1 and 2, and oxaliplatin 85 mg/m2 in a 4-6 h intravenous (i.v.) infusion before the second FUFA administration on day 2.. the most frequent side effect was grade 1-2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed.. these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gastrointestinal Diseases; Gemcitabine; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neurotoxicity Syndromes; Organoplatinum Compounds; Stomach Neoplasms; Survival Rate

To investigate the efficacy and safety of combining weekly paclitaxel with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV, folinic acid) in the treatment of patients with advanced gastric cancer. Patients with histologically confirmed recurrent or metastatic gastric cancer were studied. Paclitaxel 80 mg/m2 3-hour intravenous infusion was given on days 1, 8, and 15, and high-dose 5-FU 2,600 mg/m2 plus LV 300 mg/m2 24-hour intravenous infusion (HDFL) was given on days 2, 9, and 16, repeated every 4 weeks. Between August 1997 and August 2003, 30 patients were enrolled. The median age was 58 years (range: 37-70). Eighteen patients (60.0%) had recurrent or metastatic disease and 12 patients had de novo metastatic disease. Among the 27 patients evaluable for tumor response, 2 achieved complete response and 9 achieved partial response, with an overall response rate of 40.7% (95% confidence interval, CI: 22-61%). Eleven of the 21 patients without prior exposure to HDFL-containing regimens responded (response rate: 52.4%, 95% CI: 29-74%), while none of the 6 patients who had previously failed HDFL-containing regimens responded (p value = 0.054 by Fisher's exact test). All 30 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 6 and 10 months, respectively. Major grade 3-4 toxicities were neutropenia in 12 patients (40.0%), diarrhea in 10 patients (33.3%), and stomatitis in 3 patients (10.0%). Grade 1-2 and 3-4 paclitaxel-related neuropathy developed in 16 (53.3%) and 2 (6.7%) patients, respectively. None of the patients discontinued protocol treatment because of paclitaxel-related neuropathy or developed HDFL-related hyperammonemic encephalopathy. This paclitaxel-HDFL regimen is effective and well tolerated in the treatment of advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Prospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer.. Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m2 d1, 5FU 800 mg/m2 d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection.. Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported.. The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Stomach Neoplasms; Survival Analysis

Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate (CF)/5-fluorouracil (5-FU), Taxol plus oxaliplatin (OXA), and CF/5-FU plus cisplatin (DDP) on advanced gastric cancer, and analyze their toxicities.. Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU+DDP (control), CF/5-FU + Taxol, and Taxol + OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria.. A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate (RR) of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU+Taxol and Taxol+OXA groups than in control group (50.00% and 80.00% vs. 20.75%, P<0.05; 65.96% and 85.71% vs. 36.36%, P<0.05). But the RR of the patients with liver metastasis was similar among the 3 groups (28.57% and 39.13% vs. 34.62%, P>0.05). The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 (5.88%) patients in study group, and 3 (2.52%) of them were serious. There was no treatment-related death.. Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU + DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; Thrombocytopenia

The aim of this study was to compare the longitudinal quality of life (QoL) between LV5FU2-irinotecan and LV5FU2 alone or LV5FU2-cisplatin in a randomized Phase II trial in patients with metastatic gastric adenocarcinoma.. Among 134 eligible patients, QLQ-C30 scores were collected and described at each 2 monthly follow-up visit during 6 months. The frequencies of QLQ-C30 score improvement were calculated and mixed models for repeated measurements were applied with or without extreme poorest imputation for missing scores. The "survival" until definitive global health score (GHS) deterioration was estimated.. At the 3rd follow-up, patients with a stable or improved global health ranged from 11% in the LV5FU2-cisplatin arm to 18% in the LV5FU2-irinotecan arm. The irinotecan-based-therapy presented 14 to 15 scores with a better QoL. The time until definitive GHS deterioration was globally similar between treatment arms.. This study highlights a better impact of LV5FU2-irinotecan and the interest of QoL assessment in phase II trials to complement the risk-benefit judgement.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Female; Fluorouracil; Health Status; Humans; Irinotecan; Leucovorin; Longitudinal Studies; Male; Middle Aged; Quality of Life; Stomach Neoplasms; Survival Analysis

The purpose of this study was to assess the efficacy and toxicity of irinotecan and 5-fluorouracil (5-FU) in primary refractory or relapsed locally advanced or metastatic oesophagogastric (O-G) carcinoma.. Patients with documented progression on or within 3 months of chemotherapy were recruited between July 2000 and May 2002. Irinotecan (180 mg/m(2)) was given with 5-FU (400 mg/m(2) bolus) and leucovorin (folinic acid) (125 mg/m(2)) followed by 5-FU (1200 mg/m(2) infusion over 48 h) every 2 weeks. Response confirmed by computed tomography was assessed at 12 and 24 weeks.. Thirty-eight of 40 registered patients (95%) were assessable. Median follow-up was 9.3 months and median age was 59.0 years. Thirty-three patients (86.8%) had metastatic disease and 37 patients (97.4%) had previously received platinum-based chemotherapy. Overall response rate was 29% (95% confidence interval 15.4% to 45.9%) while an additional 34% had stable disease. Improvement in tumour-related symptoms included dysphagia 78.6%, reflux 60.0%, pain 54.5%, anorexia 64.3% and weight loss 72.7%. Grade 3/4 toxicities were anaemia 13.2%, neutropenia 26.4%, febrile neutropenia 5.2%, stomatitis 2.6%, nausea and vomiting 13.2% and diarrhoea 7.9%. Median failure-free survival was 3.7 months and median overall survival was 6.4 months.. 5-FU/irinotecan is a valuable regimen for second-line treatment in 5-FU/platinum-resistant O-G carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Squamous Cell; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms; Treatment Outcome

The main objective of this study was to determine the feasibility and the antitumor activity of a chemotherapy regimen with a 48-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), cisplatin (CDDP), and epirubicin (EPIDX) administered every 3 weeks in patients with locally advanced or metastatic gastric cancer. Thirty-three patients received CDDP 60 mg/m2 over 30 minutes followed by 1-LV 250 mg/m2 over 2 hours followed by EPIDX 60 mg/m2 over 5 minutes (bolus) and followed by 5-FU 3,800 mg/m2 as a 48-hour semiintermittent continuous infusion, with 67% of total daily dose administered between 4 pm and midnight. Four patients had a locally advanced disease and 29 had metastatic disease. A total of 171 cycles were administered. Most relevant toxicities were stomatitis (grade III in 2% of cycles and 12% of patients) and neutropenia (grade III-IV in 8% of cycles and 28% of patients) with 3 (9%) patients experiencing 1 episode of febrile neutropenia. No toxic deaths occurred. Thirty-one patients were evaluable for response. In 3 patients (9.6%) a complete response and in 11 patients (35.4%) a partial response was observed, for an objective response rate of 45% (95% C.I. 27-64%). Median progression-free and overall survival were 5.9 and 9.8 months, respectively. In conclusion, this regimen is feasible in an outpatient setting with acceptable and manageable toxicities, and it is associated with promising antitumor activity, time to progression, and survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis

To evaluate the toxicity and activity of infusional fluorouracil (FU), folinic acid (FA), and oxaliplatin, administered every 2 weeks in patients with metastatic gastric cancer.. Forty-one previously untreated patients with measurable adenocarcinoma of the stomach were eligible for the study. Patients received FU 2.6 g/m(2) (24-hour continuous infusion), FA 500 mg/m(2) (2-hour intravenous infusion), and oxaliplatin 85 mg/m(2) (2-hour intravenous infusion) every 2 weeks for 6 weeks. Treatment was continued until progression of disease was observed.. All patients were assessable for toxicity and 37 of 41 patients were assessable for response. Patient characteristics were: sex (male, 28; female,13), median age 60 years (range, 20 to 77 years), and median Eastern Cooperative Oncology Group performance status of 1. Response was evaluated every 6 weeks. Of 37 assessable patients, one complete and 15 partial remissions were observed (overall response rate, 43%). Stable disease was observed in 12 patients (32%) and progressive disease in nine patients (24%). The median overall survival was 9.6 months. WHO grade 3 or 4 hematologic toxicities included neutropenia in two patients (4.9%) and thrombocytopenia in one patient (2.4%). Other WHO grade 3 or 4 toxicities included diarrhea in three patients (7.3%) and vomiting in two patients (4.9%). There were no cases of grade 3 peripheral neuropathy and no treatment-related deaths.. Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Germany; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate

The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer.. Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both. Surgical resection was either total or partial gastrectomy according to the site of the tumor, and surgeons were allowed to perform either D1 or D2 gastrectomy. The subjects were random assigned in two treatment groups as follows: surgery alone as the control group, or surgery and adjuvant chemotherapy. Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group. The protocol included a daily administration of 200 mg/m(2) of folinic acid, 5-fluorouracil (375 mg/m(2) during the first session increasing 25 mg by session until reaching 500 mg/m(2)) and CDDP 15 mg/m(2). Two hundred patients were required. Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods.. In all, 205 patients were enrolled in the study; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy. The patients' characteristics were similar except for the mean age, which was 4 years less in the control group. Because of toxicity, 54% of the patients stopped the protocol before the end of the nine courses, and 46% of the patients received the nine courses including 32% with a decreased dose and 14% with a full dose. The 5-year survival rate was 39% in the control group and 39% in the chemotherapy group.. This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Staging; Probability; Risk Assessment; Statistics, Nonparametric; Stomach Neoplasms; Survival Analysis; Treatment Outcome

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Female; Filgrastim; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Neoadjuvant Therapy; Recombinant Proteins; Stomach Neoplasms; Thrombocytopenia; Treatment Outcome

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (FU) plus folinic acid (FA) is an effective treatment for metastatic gastrointestinal cancer. Anthracyclines are commonly used in the treatment of upper gastrointestinal cancer. The aim of this study was to determine the maximum tolerated dose of liposomal, pegylated doxorubicin (Caelyx) in combination with infusional 5-FU/sodium FA and MMC. Escalating doses of Caelyx (15-25-30-35 mg m(-2) corresponding to dose levels I-IV) were applied on days 1 and 29, given to fixed doses of 24-h 5-FU (2000 mg m(-2)) and sodium FA (500 mg m(-2), mixed with 5-FU in one pump) weekly for 6 weeks, and MMC 7 mg m(-2) on days 8 and 36. At least three patients were treated at each dose level. A total of 25 patients are evaluable. No dose-limiting toxicity (DLT) was observed on level I (n=3). On level II, DLT occurred in three out of five patients (mucositis and leucopenia). Owing to the early DLTs at this dose, we added a 20 mg m(-2) Caelyx dose level (Ia). In total, 17 patients were treated at this dose level. Among these, only two patients experienced DLT in cycle one and 37 complete cycles have been administered in association with a low toxicity profile. The median dose intensity was 100% for each drug during the first course and no treatment delay exceeding 7 days was required. The recommended dose of 4-weekly Caelyx in combination with weekly 24-h 5-FU/sodium FA and 4-weekly MMC is 20 mg m(-2). Preliminary antitumour activity has been observed in patients with pretreated pancreatic cancer and in untreated gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangiocarcinoma; Doxorubicin; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liposomes; Male; Maximum Tolerated Dose; Middle Aged; Mitomycin; Pancreatic Neoplasms; Stomach Neoplasms; Survival Analysis; Treatment Outcome

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Stomach Neoplasms; Survival Rate; Treatment Failure

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Nervous System; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma.. Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted.. Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = <.01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There were two treatment-related deaths.. Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Folic Acid; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Radiotherapy; Stomach Neoplasms; Survival Analysis; Treatment Outcome

To evaluate the efficacy of postoperative intraperitoneal hyperthermic chemoperfusion (IHCP) combined with intravenous chemotherapy for advanced gastric cancer.. Eighty-two patients with stage II - IV gastric cancer were postoperatively randomized into two groups; 46 patients in treatment group who received IHCP combined with intravenous chemotherapy for three times and 36 patients in control group who received intravenous chemotherapy only for six times. All patients in the two groups received the same chemo-regimen LFAP (CF + 5-Fu + THP or MIT + PDD) 21 - 28 days after operation.. The 1-year survival rate was 98% (45/46) in the treatment group and 94% (34/36) in the control group without any significant difference (P > 0.05). The 3-year survival rate was 83% (38/46) in the treatment group and 61% (22/36) in the control group with significant difference (P < 0.05). Gastrointestinal reaction in the treatment group was significantly decreased compared with in the control group (37% vs 80%, P < 0.01), whereas no statistically significant difference was noted in bone marrow suppression (P > 0.05).. Intraperitoneal hyperthermic chemoperfusion combined with intravenous chemotherapy can prolong survival and reduce gastrointestinal side-effect which provides an effective treatment option for advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Injections, Intravenous; Leucovorin; Male; Middle Aged; Mitoxantrone; Neoplasm Staging; Postoperative Period; Stomach Neoplasms; Survival Rate

The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting.. The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration.. Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%).. Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Female; Fluorouracil; Humans; Japan; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate

To determine the efficacy and safety of a biweekly regimen of leucovorin (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric adenocarcinoma and to select the best arm for a phase III study.. One hundred thirty-six patients (two were ineligible) were enrolled onto the randomized multicenter phase II trial. Patients received LV 200 mg/m(2) (2-hour infusion) followed by FU 400 mg/m(2) (bolus) and FU 600 mg/m(2) (22-hour continuous infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50 mg/m(2) (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180 mg/m(2) (2-hour infusion) on day 1 (arm C).. The overall response rates, which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to 23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms A, B, and C, respectively. Median progression-free survival and overall survival times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to 11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months) and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively; and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3 months) with LV5FU2-irinotecan, respectively.. Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.

Topics: Adenocarcinoma; Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Female; Fluorouracil; France; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Quality of Life; Stomach Neoplasms; Survival Analysis; Survival Rate; Treatment Outcome

To identify the most effective of two combinations, irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) and irinotecan/cisplatin, in the treatment of advanced gastric cancer, for investigation in a phase III trial.. Patients were randomized to receive irinotecan [80 mg/m2 intravenously (i.v.)], FA (500 mg/m2 i.v.) and a 22-h infusion of 5-FU (2000 mg/m2 i.v.), weekly for 6 weeks with a 1-week rest, or irinotecan (200 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.), on day 1 for 3 weeks.. A total of 115 patients were eligible for analysis in the per-protocol population. The overall response rate in the irinotecan/5-FU/FA arm (n=59) was 42.4%, with a complete response rate of 5.1%. Corresponding figures for the irinotecan/cisplatin arm (n=56) were 32.1% and 1.8%, respectively. The median time to progression was 6.5 months (irinotecan/5-FU/FA) and 4.2 months (irinotecan/cisplatin) (P < 0.0001), with median survival times of 10.7 and 6.9 months, respectively (P=0.0018). The major toxicity was grade 3/4 neutropenia, which was more pronounced with irinotecan/cisplatin than with irinotecan/5-FU/FA (65.7% versus 27%). Diarrhea was the main grade 3/4 non-hematological toxicity with both irinotecan/5-FU/FA (27.0%) and irinotecan/cisplatin (18.1%).. Both combinations were active, with acceptable safety profiles. Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neutropenia; Stomach Neoplasms; Treatment Outcome

To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma.. Patients with adenocarcinoma of the stomach (T(3)(-)(4)N(any) or T(any)N+), performance status

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Humans; Leucovorin; Maximum Tolerated Dose; Neoadjuvant Therapy; Neoplasm Staging; Stomach Neoplasms; Survival Rate

Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity.. Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m(2) days 1 and 15), folinic acid (200 mg/m(2) days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m(2 ) days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up.. Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity.. The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Stomach Neoplasms; Treatment Outcome

5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) and cisplatin, epirubicin, leucovorin and 5-FU (PELF) have both been reported to be superior to the combination 5-FU, doxorubicin and mitomycin C (FAM) in advanced gastric carcinoma. On the basis of the presence and dose intensity of the included agents, we hypothesised that PELF would be superior to FAMTX.. Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression.. The complete response (CR) rates to PELF and FAMTX were, respectively, 13% [95% confidence intervals (CI) 6% to 20%] and 2% (95% CI 0% to 5%; P = 0.003), and the objective response rates [CR plus partial response (PR) rates] 39% (95% CI 29% to 49%) and 22% (95% CI 13% to 30%; P = 0.009), thus significantly favouring the PELF combination. The survival rates after 12 months (30.8% versus 22.4%) and 24 months (15.7% versus 9.5%) were also higher among patients receiving PELF, but these differences were not statistically significant. The toxicities were qualitatively different but quantitatively similar. Both regimens seem to be feasible provided that careful patient monitoring is assured.. PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Confidence Intervals; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Humans; Italy; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Probability; Prognosis; Stomach Neoplasms; Survival Analysis; Treatment Outcome

We report the results of postoperative chemoradiotherapy after curative resection in gastric cancer patients.. Patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection with extensive (D2) lymph node dissection. Nodal metastases were observed in 261 (90%) patients. The chemotherapy consisted of fluorouracil 400 mg/m(2) plus leucovorin 20 mg/m(2) for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy were given 4 weeks after the completion of radiotherapy.. Of 290 patients accrued, 229 (79%) patients completed chemoradiotherapy as planned. With a median follow-up of 49 months, 114 (34%) patients have relapsed: 33 (29%) locoregional relapses, 76 (67%) peritoneal relapses and 41 (36%) distant metastases. The 5-year overall and relapse-free survivals were 60% and 57%, respectively. Tolerance was acceptable, the main toxicity being neutropenia.. This postoperative chemoradiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities. Whether this adjuvant therapy in gastric cancer patients that have undergone a D2 lymph node dissection impacts on survival or reduces the incidence of relapses remains to be studied.

Topics: Adenocarcinoma; Adult; Aged; Chemotherapy, Adjuvant; Combined Modality Therapy; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Prognosis; Radiotherapy, Adjuvant; Stomach Neoplasms; Treatment Outcome

Although 5-fluorouracil remains the mainstay of treatment for advanced gastric cancer (AGC), no standard chemotherapy regimen exists. Combinations of irinotecan with folinic acid and infusional 5-fluorouracil (5-FU) (ILF) have shown good efficacy with acceptable toxicity in patients with metastatic colorectal cancer. At present, only sparse data on ILF are available for AGC. Therefore we conducted a prospective study of this combination in 25 consecutive patients with metastatic gastric cancer. Median age was 63 years, 10 had received prior chemotherapy and 13 presented initially with peritoneal carcinosis. Treatment consisted of irinotecan 80 mg/m2, folinic acid 500 mg/m2 and infusional 5-FU 2.0 g/m2 over 24 h, given weekly for 6 weeks followed by a 1-week rest. Grade 3/4 hematologic toxicity occurred in six patients (anemia = 4, neutropenia = 1 and leukopenia = 1). Non-hematologic toxicity consisted mainly of nausea/vomiting (grade 3/4 in six patients) and diarrhea (grade 3/4 in 10 patients). The overall response rate was 20% for first- and second-line treatment, with two complete and three partial responses. Another nine patients (36%) had stable disease, for a tumor control rate of 56%. Median time to progression was 4 months, median overall survival and survival for patients with tumor control was 7 and 13 months, respectively. We conclude that ILF is a feasible outpatient regimen with manageable toxicity that provides tumor control in a high proportion of patients with advanced gastric cancer, even among those with unfavorable prognostic features.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Pilot Projects; Prospective Studies; Stomach Neoplasms

Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure.. Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50 mg/m(2), high-dose folinic acid (HD-FA) 500 mg/m(2), and HD 5-FU (HD-5-FU) 2000 mg/m(2) (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy.. Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare.. Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

The incidence of gastric cancer (GC) increases significantly after the fifth decade and palliative chemotherapy is the ultimate treatment in the majority of patients. We investigated safety and efficacy of a weekly regimen with cisplatin, fluorouracil and leucovorin as first-line chemotherapy for elderly patients with advanced GC. Chemotherapy-naive patients older than 65 years were considered eligible for study entry. Frail elderly patients were identified and excluded according to the following criteria: age >85 years, dependence in one or more activities of daily living (activities of daily living and instrumental activities of daily living scales), three or more comorbid conditions, one or more geriatric syndromes. Chemotherapy consisted of 1-day per week administration of intravenous cisplatin 35 mg m(-2), 6S-stereoisomer leucovorin 250 mg m(-2) and fluorouracil 500 mg m(-2) (PLF). Patients were re-evaluated after eight weekly cycles and six additional weekly administrations were planned for patients without disease progression. A 5-day subcutaneous filgrastim (5 mug Kg(-1) day(-1), days +1-+5) was used after the first treatment delay for neutropenia and maintained thereafter. In the whole group, the best intention-to-treat overall response rate was 43% (95% CI: 30-56%). The time to disease progression and the median survival time were 5.3 and 8.6 months, respectively. Fatigue was the commonest nonhaematologic toxicity (71% of the patients). Filgrastim was used in 30 patients who showed grade II (20 patients) or grade III (10 patients) neutropenia. Neither grade IV toxicity nor toxic deaths were observed. The weekly PLF regimen resulted safe and effective in elderly patients with advanced GC. This outpatient regimen is based on old and low-cost drugs and it may represent an alternative to new and more expensive combinations.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cost Control; Disease Progression; Drug Administration Schedule; Drug Costs; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Male; Recombinant Proteins; Stomach Neoplasms; Survival Analysis; Treatment Outcome

We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy.. Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival.. Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P =.002). This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Cisplatin; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Predictive Value of Tests; Preoperative Care; Prospective Studies; Radiopharmaceuticals; Statistics, Nonparametric; Stomach Neoplasms; Tomography, Emission-Computed

In vitro clinical research showed oxaliplatin (L-OHP) could obviously suppress the growth of gastric cancer cells in combination with most anti-cancer drugs and help these drugs to kill the tumor cells. This study was designed to evaluate the response and tolerance of oxaliplatin,leucovorin (LV), 5-fluorouracil (5-FU),and etoposide (VP-16) as first-line regimen in advanced gastric cancer, and compare with traditional chemotherapy regimen.. Forty-eight patients with advanced gastric cancer were divided into treatment group (L-OHP+LV+5-FU+VP-16) and control group(DDP+LV+5-FU+VP-16) using non-randomized method. L-OHP:135 mg/m(2), iv infusion 2 hours, d1(or DDP 20 mg, iv infusion, d1-5); LV:200 mg,iv infusion,d1-5; 5-FU:500 mg/m(2) CI 6 hours on d1-5; VP-16: 100 mg, iv infusion d1-5. Every course lasted 3-4 weeks.. The response rate was 64% (16/25) in treatment group (25 cases) and 34.8% (8/23) in control group (23 cases). The statistic difference was seen in two groups (P< 0.05, Chi-square test). The median survival and 1-year survival rate were 11.5 months and 45.6% for treatment group versus 10.5 months and 36.5% for control group. There was no statistical difference in two groups for overall survival (P >0.05, log-rank test). The main side effects were sensory neuritis in treatment group and nausea vomiting in control group. There were significant statistically differences in two groups (P< 0.05, Wilcoxon rank sum test). The other side effects were similar.. L-OHP + VP-16 + LV + 5-FU regimen is effective and well tolerable for advanced gastric carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate; Treatment Outcome

The 24-hour continuous infusion of 5-fluorouracil (5-FU) and folinic acid (FA) as part of several new multidrug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective, with low toxicity. In a previous phase II study with 3-weekly bolus 5-FU, FA and mitomycin C (MMC) we found a low toxicity rate and response rates comparable to those of regimens such as ELF, FAM or FAMTX, and a promising median overall survival. In order to improve this MMC-dependent schedule we initiated a phase II study with high-dose 5-FU/FA and 3-weekly bolus MMC.. From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24-hour 5-FU 2,600 mg/m(2) preceded by 2-hour FA 500 mg/m(2) for 6 weeks, followed by a 2-week rest period. Bolus MMC 10 mg/m(2) was added in 3-weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male/female ratio 20/13; median age 57 (27-75) years; median WHO status 1 (0-2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow-up was 11.8 months (range of those surviving: 2.7-11.8 months).. 32 patients were evaluable for response - complete remission 9.1% (n = 3), partial remission 45.5% (n = 15), no change 27.3% (n = 9), progressive disease 15.1% (n = 5). Median overall survival time was 10.2 months [95% confidence interval (CI): 8.7-11.6], and median progression-free survival time was 7.6 months (95% CI: 4.4-10.9). The worst toxicities (%) observed were (CTC-NCI 1/2/3): leukopenia 45.5/18.2/6.1, thrombocytopenia 33.3/9.1/6.1, vomitus 24.2/9.1/0, diarrhea 36.4/6.1/3.0, stomatitis 18.2/9.1/0, hand-foot syndrome 12.1/0/0. Two patients developed hemolytic-uremic syndrome (HUS).. High-dose 5-FU/FA/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Infusion Pumps; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Stomach Neoplasms; Survival Rate

The FLEP regimen (5-FU, LV, ETP, and CDDP) has been recommended as a combination chemotherapy to control advanced and recurrent gastric cancer. We performed a phase II study of this regimen in 49 patients with advanced gastric cancer.. The treatment regimen consisted of: 5-FU at 370 mg/m(2) (days 1-5, i.v. 24 h); LV at a dose of 30 mg (days 1-5, i.v. bolus); and ETP and CDDP each at 70 mg/m(2) (days 7 and 21, i.a. 2 h), which was repeated every five weeks.. The overall response rate was 40.8% (20/49 patients) and the median survival time was 12.6 months (range 1.1-41.8). The adverse events were Grade 3/4 leukocytopenia (16.3%), Grade 3/4 thrombocytopenia (8.2%), Grade 3 nausea and/or vomiting (4.1%), and Grade 3 stomatitis (2.0%).. Based on the encouraging response rate and prognosis, we recommend applying the FLEP regimen to patients with primary advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Stomach Neoplasms; Survival Rate

Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV).. Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0-2 were enrolled and received either 75 or 100 mg/m(2) docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m(2)) plus LV (500 mg/m(2)), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles.. Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare.. Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Disease Progression; Docetaxel; Female; Fluorouracil; Humans; Incidence; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Paclitaxel; Severity of Illness Index; Stomach Neoplasms; Survival Analysis; Taxoids; Time Factors; Treatment Outcome

To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks.. A total of 31 patients with chemo-naive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD.. A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5-81.6%). Responses were observed at all dose levels.. Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Female; Fluorouracil; Gastrointestinal Diseases; Hematologic Diseases; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Paclitaxel; Stomach Neoplasms; Taxoids

To evaluate the efficacy and safety of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FA) combination in patients with metastatic or advanced gastric cancer (M/AGC).. Of the 54 eligible patients with measurable or assessable M/AGC, 53 received oxaliplatin 100 mg/m(2) and FA 400 mg/m(2) (2-hour intravenous infusion) followed by 5-FU bolus 400 mg/m(2) (10-minute infusion) and then 5-FU 3,000 mg/m(2) (46-hour continuous infusion) every 14 days.. Patients (69% male, 31% female) had a median age of 61 years (range, 31 to 75 years), 89% had a performance status of 0 or 1, 70% had newly diagnosed disease, and 87% had metastatic disease. All had histologically confirmed adenocarcinoma. With a median of three involved organs, disease sites included the lymph nodes (67%), stomach (65%), and liver (61%). A median of 10 cycles per patient and 468 complete cycles were administered. Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving an overall best response rate of 44.9%. Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy). Median follow-up, time to progression, and overall survival were 18.6 months, 6.2 months, and 8.6 months, respectively. Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and anemia occurred in 38%, 19%, 4%, and 11% of patients, respectively, and febrile neutropenia occurred in six patients (one episode each). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity.. This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable safety profile in M/AGC patients, and may prove to be a suitable alternative regimen in this indication.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Gastric carcinoma remains one of the leading causes of cancer-related death in the world. Clinical studies have revealed that approximately two thirds of the patients seek treatment for early recurrence within the abdominal cavity. The aim of this phase II study was to evaluate the toxicity, feasibility, and efficacy of adjuvant intraperitoneal chemotherapy (IPCT) with cisplatin, mitoxantrone, 5-fluorouracil (5-FU), and folinic acid in patients with stage II-III gastric cancer. Patients with stage II and III gastric cancer aged between 15 and 70 years, after curative resection, with adequate liver, renal, and cardiac function were included in the study. The chemotherapy regimen consisted of cisplatin 60 mg/m2, mitoxantrone 12 mg/m2, 5-FU 600 mg/m2, and folinic acid 60 mg/m2, delivered intraperitoneally, diluted in 2 l normal saline. Intraperitoneal fluid was not drained. Each course of IPCT was repeated every 4 weeks for a total 6 cycles. Thirty-nine patients were enrolled in the study. Twenty-eight of the 39 patients (71.8%) completed six courses of the planned schedule. One patient (2.6%) died after a fourth cycle of IPCT from an undetermined reason. The major nonhematologic toxicity from IPCT was grade I-III nausea and/or vomiting experienced by 27 patients (69.2%). Twenty-four (61.5%) patients reported abdominal discomfort. Median follow-up was 23 (range: 3-105) months. Twenty-five patients (64.1%) were dead. Median disease-free survival and overall survival were 12 (CI 95%; 8.3-15.7 months) and 19 months (CI 95%; 10.5-27.5 months), respectively. The cumulative 5-year disease-free survival and overall survival were 24.7% and 30.7%, respectively. The regimen was generally associated with acceptable toxicity. However, adjuvant IPCT has similar survival rates in comparison to no adjuvant treatment; thus, it cannot be currently recommended outside the context of a clinical trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Mitoxantrone; Stomach Neoplasms; Survival Analysis

In an open prospective study with matched historical controls we aimed to evaluate whether a polysaccharide fraction isolated from the herb Echinacea purpurea could counteract the undesired effects of chemotherapy. Fifteen patients with advanced gastric cancer undergoing palliative chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) received for 10 days (beginning 3 days before chemotherapy) daily i.v. injections of 2 mg of a polysaccharide fraction isolated from Echinacea purpurea herb cell cultures (EPS-EPO VIIa). The median number of leukocytes 14-16 days after chemotherapy was 3630/microL (range 1470-5770) in the patients receiving EPS-EPO VIIa compared with 2370/microL (870-3950) in the patients of the historical control group (p = 0.015). EPS-EPO VIIa had no clinically relevant effects on phagocytic activity of granulocytes or on lymphocyte subpopulations. Sixty-eight adverse events including two deaths were observed, most likely due to chemotherapy and the general condition of the patients. However, an association with the test intervention cannot be ruled out completely. The results of this pilot study suggest that EPS-EPO VIIa might be effective in reducing chemotherapy-induced leukopenia. The efficacy and safety should be investigated in further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cells, Cultured; Echinacea; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Lymphocytes; Male; Middle Aged; Phytotherapy; Pilot Projects; Plant Extracts; Polysaccharides; Stomach Neoplasms; Treatment Outcome

The combination of etoposide, folinic acid, and 5-fluorouracil (5-FU) (ELF regimen) has been proved to be an active chemotherapy in patients with advanced gastric cancer. The aim of this study was to confirm the efficacy in the clinical setting and to correlate response with different parameters like serum tumor markers. We treated 60 patients with advanced gastric cancer with 120 mg/m2 etoposide, 300 mg/m2 folinic acid, and 500 mg/m2 5-FU, on d 1-3. The cycle was repeated on d 21. Objective response was obtained in 23% of all patients with measurable disease. Stable disease was obtained in 37%. The tumor-growth-control rate in patients with proximal carcinoma was significantly higher than in those with distal carcinoma (85% vs 48%, p = 0.04). Median survival for all patients was 8.0 mo (95% confidence interval [CI] 7.0-8.5). In responsive patients, survival was more than two-fold longer than in patients with progressive disease. The administration of ELF could be performed safely on an outpatient basis. Toxicity was rather mild. The most frequently elevated serum tumor marker was CA 72-4 (55% of the patients). An elevated level of carcinoembryonic antigen before treatment was significantly correlated with progressive disease. A more than two-fold elevation of at least one marker under treatment was significantly correlated to progressive disease (p < 0.002). A reduction of at least one marker under treatment was significantly correlated to tumor growth control (p < 0.00015). The results of the present trial confirm the efficacy and low toxicity of the ELF regimen in advanced gastric carcinoma. Serum tumor markers proved suitable parameters for assessing response to treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease-Free Survival; Etoposide; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Prognosis; Stomach Neoplasms; Survival Rate; Treatment Outcome

The aim of this study was to evaluate the toxicity and efficacy of combination chemotherapy with weekly 24-h continuous infusion of 5-fluorouracil (5-FU)/folinic acid, weekly paclitaxel and 3-weekly cisplatin in patients with unresectable, locally advanced or metastatic gastric adenocarcinoma. Between November 1999 and November 2001, 29 chemotherapy-naive patients (13 male and 16 female) with a median age of 56 years (range 22-72) were consecutively enrolled at three centers. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2-h infusion. Paclitaxel 80 mg/m2 was administered as a 1-h infusion weekly and cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was considered one cycle. A median of 3 cycles (range 1-5) was administered to 29 patients with a total of 73 cycles applied. All patients were assessable for toxicity and survival, 28 patients were assessable for response (one patient received less than one complete cycle and could not be evaluated for response). Four patients (14%) obtained a complete response and 10 patients (34%) a partial response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had stable disease. Seven patients (24%) had progressive disease during or within 4 weeks after treatment. The median progression-free and overall survival times were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall toxicity was acceptable. Hematological toxicity was favorable with only one patient (3%) experiencing WHO grade 3/4 leukocytopenia and one patient (3%) WHO grade 3/4 anemia. Non-hematologic WHO grade 3/4 toxicities included alopecia in 19 (66%), nausea/vomiting in six (21%), diarrhea in six (21%), neurotoxicity grade 3 in three (10%) and infection in three (10%) patients. A total of 42 applications (10%) (range 0-5) had to be postponed and dose reductions of at least one drug was necessary in 37% of applications. In three patients (10%) treatment was stopped because of toxicity. All patients were treated on an outpatient basis. Thus, the combination of weekly paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of patients with advanced gastric cancer. Compared with our previous experience with the same combination of drugs but using paclitaxel at 175 mg/m2 given every 3 weeks, the protocol with weekly application of paclitaxel 80

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Hematologic Diseases; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Stomach Neoplasms; Survival Rate; Time Factors

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Therapy, Combination; Epirubicin; Fatigue; Female; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Injections, Subcutaneous; Leucovorin; Male; Middle Aged; Neutropenia; Paclitaxel; Stomach Neoplasms; Taxoids; Thrombocytopenia; Treatment Outcome

Adjuvant chemotherapy of gastric cancer after curative resection is still subject to discussion. In this study 137 patients with gastric adenocarcinoma, all with positive nodes, were randomized after curative resection so that 69 received epidoxorubicin (EPI), leucovorin (LV) and 5-fluorouracil (5-FU) on days 1-3 every 3 weeks for 7 months, whereas the remaining 68 did not. After a follow-up period of 5 years, 21 of the 69 treated patients (30%) and nine controls (13%) were still alive; median survival time was 18 months for the controls and 31 months for the patients treated with adjuvant chemotherapy (P< 0.01).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Stomach Neoplasms

The results of chemotherapy for patients with gastric carcinoma generally have been modest, although regimens developed more recently have produced higher response rates. One such regimen is epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (ECF). The advantage of a long-term oral administration of uracil and tegafur (UFT) is that this treatment may be used to mimic the protracted infusion of 5-fluorouracil (5-FU). In addition, UFT treatment combined with leucovorin had a favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. Instead of the inconvenience of an infusion pump and intravenous catheter for the protracted infusion of 5-FU, the authors administered UFT plus leucovorin in an ECF regimen for the treatment of patients with advanced gastric carcinoma.. Fifty-two patients with advanced gastric carcinoma received epirubicin, cisplatin, and oral UFT plus leucovorin. Epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered on Day 1 by intravenous injection. Tegafur and uracil 360 mg/m(2)/day orally was administered in conjunction with leucovorin administered at a fixed dose of 45 mg/day orally in divided daily doses for 21 days followed by a 7-day rest period. These courses were repeated every 4 weeks. The median age of the patients was 59 years with a median World Health Organization performance status of 1. Patients received a median of five courses of treatment (range, 1-10).. Among the 47 patients evaluated, three patients achieved complete response, and 24 patients had partial responses, for an overall response rate of 57.5% (95% confidence interval, 71.5-43.3%). Stable disease was reported in 11 patients (23.4%), and another 9 patients (19.1%) showed disease progression. The median duration of survival was 15 months (range, 2-33+). The main toxicity was nausea/vomiting and neutropenia. Significant toxicity (modified National Cancer Institute common toxicity Grade 3 or 4) included neutropenia in 22 patients (42%), nausea in 14(27%), vomiting in 9 (18%), oral mucositis in 3 (6%), and diarrhea in 3 (6%) patients.. The authors conclude that epirubicin, cisplatin, and oral UFT plus leucovorin, a convenient regimen, has a significant activity and tolerable toxicities in patients with gastric carcinoma.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Drug Administration Schedule; Drug Tolerance; Epirubicin; Female; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Tegafur; Treatment Outcome; Uracil

A phase II study was performed to evaluate 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) and leucovorin as first-line chemotherapy in European patients with advanced gastric cancer. From 38 patients, 25 were evaluable for response and 36 for toxicity. Patients received UFT at 300 mg/m(2)/day for 28 days, every 35 days and leucovorin at 90 mg/day on an identical schedule. Overall response rate was 10.5% (95% confidence interval (CI): 3.7-22.5%) in intent-to-treat analysis and 16% (95% CI: 5.7-33%) in evaluable patients. Grade 3-4 common toxicity criteria (CTC) toxicities were diarrhoea (28%; 10/36), nausea (11%; 4/36), vomiting (8%; 3/36) and asthenia (11%; 4/36). 23 patients in 44% (42/96) of the courses had to skip days of treatment due to toxicity or to non-compliance. In conclusion, UFT+leucovorin has a definitive, but low, efficacy in advanced gastric cancer patients. Toxicities were mainly gastrointestinal and treatment needs to be withheld if grade 2 diarrhoea occurs.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.. A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart.. The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent.. Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Disease-Free Survival; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Radiation Dosage; Stomach Neoplasms; Survival Rate

In patients with non-colon digestive carcinomas, various schedules and doses of 5-fluorouracil (5-FU) and leucovorin combined with cisplatin (CDDP) have been used extensively. The present study explored the toxicity and activity of a weekly 24-h infusion of high dose 5-FU modulated by high dose leucovorin with bi-weekly CDDP. 59 patients with measurable disease were treated with a weekly infusion of high dose 5-FU (2 or 2.6 g/m2)+leucovorin 500 mg/m2 for 6 weeks and a bi-weekly dose of CDDP (50 mg/m2). All patients had metastatic or locoregionally advanced disease and had a performance status < or =3. All patients were evaluable for toxicity and 58 for response. Toxicity was different according to the schedule of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2.6 g/m2 with a high incidence of grade 3/4 neutropenia (16%) and febrile neutropenia (13%), and led to dose reductions in both CDDP and 5-FU in 13 patients (34%). For patients who started 5-FU at a dose of 2 g/m2, no reduction in 5-FU was required, and only 4 patients required a dose reduction of CDDP (19%). Grade 3/4 neutropenia was seen in 10% of patients of this group and only 1 patient required hospitalisation for febrile neutropenia. Other grade 3/4 toxicities were rare in both groups. Renal toxicity was infrequent and mild and did not require dose adjustments. The overall response rate was 33%; 19 patients achieved a partial responses (PR). No patient had a complete response (CR). The median duration of response was 5.7 months (range 2-24 months) and the median survival was 7.9 months ( range: 1-30, 95% confidence interval (CI): 7-9). The combination of weekly 24-h infusion of high dose 5-FU with leucovorin and bi-weekly cisplatin seems a well-tolerated and active treatment in non-colon digestive carcinomas. A dose of 2 g/m2 of 5-FU seems to be recommended.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Digestive System Neoplasms; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Pancreatic Neoplasms; Stomach Neoplasms; Treatment Outcome

Neoadjuvant chemotherapy was applied to patients with advanced gastric cancer and confirmed para-aortic lymph node metastasis. Subjects were 7 patients. The response to the neoadjuvant chemotherapy was a PR in 5 cases, MR in 2 cases for the primary lesion and CR in 2 cases PR in 5 cases for the para-aortic lymph node metastasis. The grades of histological response assessed on the resected specimen were Grade 0 in three cases, Grade 1a in one, Grade 1b in one and Grade 2 in two. While there was no significant difference in survival rate between patient groups with and without neoadjuvant chemotherapy, the 2-year survival rate in patients with neoadjuvant chemotherapy was a good 42.9%, compared with 10% in patients groups without neoadjuvant chemotherapy. It is concluded that a better prognosis can be expected for advanced gastric cancer patients with neoadjuvant chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Stomach Neoplasms; Survival Rate

The FLEP regimen (5-FU, LV, ETP and CDDP) is a combination chemotherapy administered regionally and systemically for the control of both local and disseminated disease in intra- and extra-abdominal regions in patients with advanced and recurrent gastric cancer. Sixty-one patients with advanced and recurrent gastric cancer were entered into this study. The treatment regimen consisted of 5-FU at 370 mg/m2 (days 1 to 5, i.v. 24 h); LV at a dose of 30 mg (days 1 to 5, i.v. bolus); and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 36.1% (22/61) and the 50% and median survival times were 10.23 and 11.80 months, respectively. The adverse events were Grade 3/4 leukocytopenia (18.0%), Grade 3/4 thrombocytopenia (4.9%), Grade 3 nausea and/or vomiting (3.3%) and Grade 3 stomatitis (1.6%). Of the 17 NAC patients, the six curability B patients showed a statistically higher survival rate than the curability C and unresected patients. Based on the encouraging response rate and the improvement in prognosis, we recommend the FLEP regimen for patients with primary gastric cancer. Neoadjuvant chemotherapy using the FLEP regimen should be performed with curative resection as an objective.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Rate

A phase II study testing the safety and efficacy of irinotecan (CPT-11). 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with advanced gastric adenocarcinomas.. Patients with metastatic or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach were entered onto this study. Previous chemotherapy for metastatic disease was not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125 mg/m2 intravenously (i.v.) followed immediately by LCV 20 mg/m2 i.v. and 5-FU 500 mg/m2 i.v., all given weekly for four weeks followed by a two-week rest.. Thirty-eight patients were enrolled and 36 eligible patients received protocol therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3 (8%) dying of neutropenic sepsis. The overall response rate was 22% (95% confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and median time to progression was 4.4 months.. This weekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and diarrhea were similar to those observed historically in patients receiving this regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more frequent, and dose modifications were substantial. Future trials of this combination in patients with gastric cancer should decrease the absolute starting drug doses and/ or employ altered scheduling that better accommodates the pattern of toxicity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophagogastric Junction; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Stomach Neoplasms; Survival Rate; Treatment Outcome

The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer.. Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery.. A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls.. Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.

Topics: Adenocarcinoma, Scirrhous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Neoadjuvant Therapy; Stomach Neoplasms; Survival Rate; Treatment Outcome

A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer.. From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break.. There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively.. This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Rate

Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported.. Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated.. From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse.. EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.

Topics: Acute Disease; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disseminated Intravascular Coagulation; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Stomach Neoplasms; Survival Rate

We performed combination chemotherapy adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in 11 patients with gastric cancer and 7 with colorectal cancer. Treatment consisted of a 5-day course of continuous arterial or intravenous infusion of 5-FU (500 mg/body/day), arterial or intravenous infusion of leucovorin (20 mg/body/day) at 6:00 p.m. on days 1-5, arterial or intravenous infusion of mitomycin C (2 mg/body) at 9:00 a. m. on day 5, and arterial or intravenous infusion of cisplatin (20-80 mg/body) at 6:00 p.m. on day 5. The effective rate against gastric cancer was 73%; however, the effective rate against colorectal cancer was 29%. During and after this therapy, there was only a little appetite loss, nausea and stomatitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Mitomycin; Stomach Neoplasms; Survival Analysis

To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer.. A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points.. The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX).. All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Methotrexate; Middle Aged; Proportional Hazards Models; Stomach Neoplasms; Survival Analysis

This study was performed to investigate the activity and safety of high dose 5-fluorouracil (5-FU) given as a weekly 24-hour infusion in combination with folinic acid plus mitomycin C in patients with advanced gastric cancer.. Chemonaive patients with locally advanced inoperable, recurrent or metastatic gastric cancer were treated with 15 mg/m(2) i.v. mitomycin C as bolus on day 1 of a 7-week cycle followed by a 2-hour infusion of folinic acid (500 mg/m(2)) and a 24-hour infusion of 5-FU (2,600 mg/m(2)) given on days 1, 8, 15, 22, 29, and 36 as outpatient treatment.. Thirty evaluable patients (median age 58 years and median ECOG performance status 1) received 1-4 cycles (median 3). 53% of the patients had liver metastases. Treatment-related toxicity was low with 10% of patients experiencing diarrhea >/=grade 3, 3% mucositis grade 3 and 3% nausea grade 3 (CTC). Hematological toxicity was mild with 13% thrombopenia grade 3 and no leukopenia grade 4. Eleven patients achieved a partial remission (major response rate 37%; 95% confidence interval 22-53%). Median time to progression was 5 months and median overall survival time was 7 months.. This regimen is a well-tolerated outpatient treatment for patients with advanced gastric cancer with efficacy being comparable to other chemotherapy protocols.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Stomach Neoplasms

The aim of this study was to determine the role of concomitant chemoradiation in the alleviation of obstructive jaundice in patients with extrahepatic biliary tract metastases from gastric carcinoma.. Thirteen patients with good performance status who had obstructive jaundice resulting from extrahepatic biliary metastases after gastrectomy for gastric carcinoma were treated with palliative intent. Treatment consisted of insertion of a percutaneous transhepatic choledochal drainage (PTCD) catheter followed by external radiation up to a total dose of 40-60 grays in combination with chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an outpatient basis.. The concomitant chemoradiation produced a good palliative effect in all 13 patients. Hyperbilirubinemia continued to improve after treatment, patients' clay-colored stool resolved within an average of 4 weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD catheter could be removed after treatment was completed (the seventh week); the mean duration of PTCD placement was 2 months. The entire treatment course was performed on an outpatient basis; hospital admission was necessary only for PTCD insertion and chemotherapy. Ten patients died of their disease, with an average survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion. Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was maintained until death. No serious treatment-related complications occurred, and no endoprothesis or intraluminal brachytherapy was needed in this study.. Satisfactory palliation can be achieved by concomitant chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma, providing an alternative treatment choice for these patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Brachytherapy; Cholestasis, Extrahepatic; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Palliative Care; Recurrence; Stomach Neoplasms; Treatment Outcome

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis

Adenocarcinoma of the stomach and gastroesophageal junction results in substantial morbidity, locoregional recurrence, and death. Surgical procedures, even with adjuvant therapy, have not significantly improved survival. This study evaluated the toxicity, response rate, locoregional control, and survival of patients with locally advanced gastric cancer that was treated with neoadjuvant multimodality therapy.. Patients with stage IIIA or early stage IV gastric adenocarcinoma received neoadjuvant 5-fluorouracil, Leucovorin, Adriamycin, and Cisplatin and underwent gastrectomy or esophagogastrectomy with intraoperative radiotherapy (IORT; 1000 cGY) to the gastric bed and postoperative radiation therapy.. Nine of 15 patients (60%) with transmural extension and/or nodal metastases received IORT. There were 2 pathologically complete responses at the primary site. Eleven of 15 patients (73%) had tumor in perigastric lymph nodes; however, 9 of 15 patients (60%) had mucin-filled nodes without tumor cells. Neoadjuvant treatment did not increase operative morbidity rates. Ten of 15 patients (67%) remain free of disease (median, 27 months; range, 6-60 months). Five patients died 13 to 41 months (median, 17 months) after diagnosis.. Neoadjuvant multimodality therapy with neoadjuvant 5-fluorouracil, Leucovorin, Adriamycin, and Cisplatin, radical resection with IORT, and postoperative radiation therapy is safe, can downstage tumors, provides improved locoregional control, and appears to cause significant tumor regression that may result in long-term survival or cure.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Esophagectomy; Female; Fluorouracil; Gastrectomy; Humans; Intraoperative Care; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Survival Analysis

Combination chemotherapy with 5-FU, LV, ETP and CDDP (FLEP) for advanced gastric cancer uses a combination of regional and systemic delivery for the control of both local and disseminated disease in the intra- and extra-abdominal regions. We performed this regimen as neoadjuvant chemotherapy (NAC). Fifteen patients with unresectable primary advanced gastric cancer underwent FLEP. The treatment regimen was 5-FU at 370 mg/m2, LV at 30 mg/body (days 1 to 5, i.v. 24 h) and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 46.7% (7/15), and the 50% and median survival times were 11.43 and 12.35 months, respectively. The adverse events were Grade 3 leukocytopenia, Grade 3 thrombocytopenia, and Grade 3 stomatitis in 20.0%, 13.3%, and 6.7% of the patients, respectively. The 50% and median survival time overall were 11.43 and 12.35 months, respectively. Of the 15 NAC patients, curability B patients showed a statistically higher survival rate than curability C and unresected patients. In conclusion, FLEP was effective for unresectable advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Stomach Neoplasms

To observe the therapeutic effects and toxicity of HLF (hydroxycamptothecin HCPT/leucovorin LV/fluorouracil 5-Fu) regimen and ELF (etoposide VP-16/LV/5-Fu) regimen in middle-aged and elderly patients with advanced gastric carcinoma.. A group of twenty-five cases were treated with HLF regimen, and the other group of 23 cases were treated with ELF regimen.. Of the 25 cases treated with HLF regimen, there was no complete remission (CR), but there were 12 partial response (PR), 11 no response (NC), and 2 had progressive disease (PD). The response rate (RR) was 48.0%. Of the 23 patients treated with ELF regimen, there was no CR, there were 9 PR, 11 NC, and 3 PD. The RR was 39.1% (P > 0.05). The main toxicity was myelosuppression and stomatocace. Grade III-IV stomatocace in HLF regimen group (68.0%) was more commonly seen than that in ELF regimen group (39.1%, P < 0.05). There was no cardiac or renal toxicity observed.. HLF regimen is promising for treatment of advanced gastric carcinoma in middle-aged and elderly patients with the merits of low toxicity affecting heart, kidney and bladder except stomatocace, which is worthy of further clinical trial.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma.. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis.. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively.. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Stomach Neoplasms; Stomatitis; Treatment Outcome

The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly palliative, therefore regimens with mild toxicity and acceptable activity should be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF) is suitable chemotherapy in this situation. We have enrolled 33 patients with MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil 500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable for response, toxicity and survival. Two patients achieved complete response (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had stabilization of disease (SD) and 12 patients had disease progression (PD). The median survival for all patients was 6 months (range, 1 to 40+). ELF was well tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In conclusion, the ELF regimen in our trial demonstrated, in this kind of patient, moderate activity in the absence of relevant toxicity, confirming its suitability in patients in generally poor condition.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis

Thirty-four patients with gastric cancer in stage II and III were enrolled, after curative resection, in a pilot study to assess the feasibility and the impact on relapse of a double modulation of 5-Fluorouracil (5FU) by Methotrexate (MTX) and 1-Leucovorin (LFA) as adjuvant chemotherapy.. The schedule was: MTX 500 mg/m2d. 1, LFA 250 mg/m2d.2, 5FU 600 mg/m2d.2. Cycles were repeated every two weeks for 16 times. Quality of life during treatment was evaluated with the EORTC QLQ-C30.. At a median follow-up of 24 months, 21 (61%) patients treated with postoperative chemotherapy, were disease-free. Toxicity was primarily gastrointestinal, but its intensity was usually mild. The feasibility of treatment was also confirmed from the results of QLQ-C30 questionnaire.. This study demonstrates that the schedule tested is feasible as postoperative treatment in curatively resected gastric cancer patients and prompts the initiation of a randomized trial with a no-treatment control arm.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Pilot Projects; Stomach Neoplasms

A combination of etoposide, 5-fluorouracil, and folinic acid (ELF) remains popular for the treatment of patients with gastric carcinoma and has been reported to result in a response rate of up to 40% with good patient tolerance. The authors elected to add granulocyte-macrophage-colony stimulating factor (GM-CSF) to ELF to determine whether the response rate could be increased in patients with untreated advanced gastric carcinoma.. Previously untreated patients with measurable metastatic tumor were studied. Outpatient therapy was comprised of etoposide, 120 mg/m2 intravenously (i.v.), on Days 1-3; 5-fluorouracil, 500 mg/m2 i.v., on Days 1-3; and folinic acid, 300 mg/m2 i.v., on Days 1-3. Courses were repeated every 21 days. GM-CSF (at a dose of 250 microg/m2/day for 14 days from Day 4) was added after the first course of ELF if patients developed Grade 4 neutropenia in a previous course.. Thirty patients were enrolled and 29 were evaluable for response. Four patients (14%) achieved a partial response (median duration of response, 6.5 months). The median duration of survival was 7.8 months. Grade 4 neutropenia occurred in 16 patients who then received GM-CSF. A similar rate of neutropenic fever was observed in courses both with or without GM-CSF (15% in courses without GM-CSF and 16% in courses with GM-CSF); however, a higher nadir absolute granulocyte count (1300 cells/microL) occurred in courses with GM-CSF compared with courses without GM-CSF (300 cells/microL).. The ELF regimen resulted in a much lower response rate than reported in the literature. The attempt to improve the efficacy of this regimen by the addition of GM-CSF did not prove successful. The authors believe this regimen cannot be recommended for the treatment of patients with advanced gastric carcinoma outside of a protocol setting.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Etoposide; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Stomach Neoplasms

In the authors' previous experience, the addition of epidoxorubicin to the FA-FU regimen obtained a better response rate than that of FA-FU alone in patients with advanced gastric cancer. Furthermore, considering the good efficacy and mild toxicity observed with the addition of etoposide to the FA-FU combination in the German study, the authors conducted a trial to explore the efficacy and tolerability of the ELFE regimen (epirubicin, folinic acid, fluorouracil, and etoposide) in previously untreated advanced gastric cancer patients. Of the 55 patients entered, 51 were evaluable for efficacy. Four complete responses (8%) and 21 partial responses (41%) were observed, with an overall response rate of 49% (95% CI: 35-63%). The median duration of response and survival were 6 and 8 months, respectively. Responder patients showed a significantly better median survival duration than nonresponders (12 vs. 4 months, respectively; p < 0.0001). Toxicity was evaluated in all patients: only 1 patient refused to continue therapy despite low toxicity. As expected, the major toxicities observed were gastrointestinal disturbance, leukopenia, and loss of hair. In conclusion, the ELFE combination regimen appears to be effective and well tolerated for the treatment of advanced gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Stomach Neoplasms; Survival Analysis

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Locally advanced or metastatic adenocarcinoma of the stomach still carries a poor prognosis, with 5-year survival rates of < 15%. Palliative chemotherapeutic regimens for this disease are largely 5-FU-based. We have investigated the clinical activity of an oral combination of uracil and tegafur (UFT) with calcium folinate (Orzel), in patients with measurable metastatic disease. Thirty-six patients received a total of 94 courses of daily UFT 300 mg/m2 plus calcium folinate 90 mg for 28 consecutive days followed by a 7-day rest. Planned treatment doses were maintained in 83% of all evaluable courses. Main toxicities included diarrhea (21 patients) and nausea and vomiting (20 patients). Other side effects were asthenia, malaise, stomatitis, and myelosuppression. At present, 26 patients are evaluable for response. Of these, one achieved a complete response and three achieved partial remissions. In addition, six patients reached stable disease, yielding an overall response rate of 27%. We conclude that the combination of UFT and calcium folinate is a feasible outpatient regimen that warrants further clinical evaluation.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Feasibility Studies; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Palliative Care; Retrospective Studies; Stomach Neoplasms; Tegafur; Uracil

UFT (uracil and tegafur in a 4:1 molar ratio) plus calcium folinate treatment has favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. High response rates have been reported in patients with advanced gastric carcinoma receiving a schedule of epirubicin, cisplatin (Platinol), and protracted infusion of 5-fluorouracil (5-FU). Replacing the inconvenient infusion pump and intravenous catheter needed for protracted infusion of 5-FU, we administered oral UFT plus calcium folinate (Orzel) to 37 patients (median age, 55 years; median World Health Organization [WHO] performance status of 1) with locally advanced or metastatic gastric carcinoma. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered by intravenous injection on day 1; UFT 360 mg/m2/day po was administered in conjunction with oral calcium folinate 25 mg/m2/day in divided daily doses for 21 days, followed by a 7-day rest period. Courses were repeated every 4 weeks. Among 37 evaluable patients who received a median of four courses of treatment (range, 2 to 10), two achieved a complete response and 18 a partial response, for an overall response rate of 54% (95% confidence interval, 39% to 70%). Stable disease was reported in 12 patients (32.4%) and disease progression in another five (13.5%). The median duration of survival was 10 months (range, 2 to 15+). The main toxicities were nausea/vomiting, leukopenia, diarrhea, and oral mucositis. WHO grade 3 or 4 toxicity included leukopenia in 14 patients (37.8%), nausea/vomiting in 11 (29.7%), oral mucositis in five (13.5%), and diarrhea in four (10.8%). Epirubicin, cisplatin, and oral UFT plus calcium folinate, a convenient outpatient regimen, has significant activity and tolerable toxicities in patients with gastric carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Drug Administration Routes; Epirubicin; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Uracil

Combination chemotherapy with multiple drugs (FLMP therapy), in which the drugs were determined based on biochemical modulation and the dosing schedule was established in accordance with the circadian rhythms of the human body, was performed in cases of advanced recurrent gastric cancer. The drugs were administered according to the following schedule: 500 mg of 5-FU (continuous) on days 1-5 (the dose was increased during the night), 20 mg of LV on days 1-5 (at 6 PM), 2 mg of MMC on day 5 (at 9 AM) and 60-80 mg of CDDP on day 5 (at 6 PM). A five-day course was administered by intravenous drip or hepatic arterial infusion at intervals of 4 weeks. Of 14 patients treated, the effect was estimated to be CR in 3, PR in 6, NC in 3, and PD in 2. The effectiveness rate was 62.3% overall, and the rate by administration route was 6/10 (60.0%) for i.v. and 3/4 (75.0%) for i.a. The side effects were slight. Those of grade 3 or more included anorexia in 5%, nausea and vomiting in 1%, stomatitis in 1% and leukopenia in 1%. This therapy, administered in accordance with the theory of chronotherapy, caused few side effects, and thus is considered a promising treatment for gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Circadian Rhythm; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Remission Induction; Stomach Neoplasms

ECF (epirubicin, cisplatin, protracted venous fluorouracil) is superior to FAMTX in gastroesophageal cancer, but protracted fluorouracil adds to its morbidity and cost. In this dose-escalation pilot study, fluorouracil was replaced by oral UFT and leucovorin.. Thirty unpretreated patients with advanced upper gastrointestinal cancers received epirubicin 50 mg/m2 and cisplatin 60 mg/m2 i.v. on day 1, and leucovorin 45 mg p.o. on days 1, 8 and 15, of a 21-day cycle for up to 8 cycles. UFT was taken 12-hourly throughout, at escalating doses in four cohorts ranging from 150-325 mg/m2 per day.. The maximum tolerable dose of UFT, recommended for further study, was 200 mg/m2 per day. At higher doses, more than two-thirds patients required dose reductions, although mostly for persistent mild (CTC grade 2) nausea, diarrhoea or fatigue, rather than for severe acute toxicity. Myelotoxicity was mild. Twenty patients, including 15 with gastroesophageal cancer, had assessable disease. Among these there were nine WHO objective responses, all in gastroesophageal patients, including two radiological complete responses.. ECU is well tolerated at the defined dose, with activity comparable to ECF in gastroesophageal cancer. UFT and other oral 5FU dosing strategies make promising components of combination chemotherapy, deserving further, randomised evaluation.

Topics: Administration, Oral; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Esophageal Neoplasms; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Severity of Illness Index; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; United Kingdom

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Gastrointestinal Neoplasms; Humans; Leucovorin; Male; Middle Aged; Nausea; Stomach Neoplasms; Tegafur; Uracil; Vomiting

Sequential chemotherapy with methotrexate and 5-fluorouracil (MTX/5-FU) for advanced gastric cancer was given 29 patients. The procedure consisted of weekly MTX 100 mg/m2 (i.v.) followed three hours later by 5-FU 600 mg/m2 (i.v.) with leucovorin rescue on each of the following two days. Nine of 28 patients (32.1%) showed partial response to this treatment. Response rates were 28.6% in the 21 cases with poorly differentiated adenocarcinoma and 42.9% in the 7 cases with well- or moderately-differentiated adenocarcinoma. This procedure was especially effective for primary lesions (PR 9/20: 45%) and lymphnode metastases (CR 4 + PR 4, 8/17: 47.1%). Side effects were mild leukopenia and G-I symptoms such as nausea, diarrhea and loss of appetite, except in 1 patient who died of severe myelosuppression with sepsis. We concluded that sequential MTX/5-FU therapy is fairly effective and the adjuvant chemotherapy of choice for advanced or recurrent gastric cancer with not only poorly differentiated adenocarcinoma but also well- or moderately-differentiated adenocarcinoma.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Stomach Neoplasms

Although many drug combination therapies have been proposed, there is no standard therapy for patients with advanced gastric carcinoma. The superiority of combination therapy over monochemotherapy has not been demonstrated convincingly. To explore the role of monochemotherapy, the authors evaluated 5-fluorouracil (5-FU), modulated by 6S-leucovorin (6S-LV) and a cisplatin-containing regimen, which was comprised of epirubicin, etoposide, and cisplatin with the addition of the reversal agent lonidamine (EEP-L).. After stratification according to performance status (PS) and resection of the primary tumor, 72 patients with advanced gastric carcinoma were randomized to 2 parallel Phase II trials with 5-FU/6S-LV and EEP-L, respectively. Thirty-six patients in Study A received bolus 6S-LV, 100 mg/m2, followed by bolus 5-FU, 370 mg/m2, on Days 1-5 and 36 others in Study B received epirubicin, 30 mg/m2, on Days 1 and 5; etoposide, 100 mg/m2, on Days 1, 3, and 5; cisplatin, 30 mg/m2, on Days 2 and 4; and lonidamine, 150 mg/day.. There were 6 partial responses (18.2%) (95% confidence interval [CI] +/- 13.2) in Study A and 7 partial responses (21.9%) (95% CI +/- 14.3) in Study B. Partial responses were more frequent in patients with resected tumors or with an Eastern Cooperative Oncology Group PS of 0-1. The median duration of response was 8.8 and 8.3 months, respectively, in Study A and Study B. The median survival reached 8 months in Study A and 9 months in Study B. In the whole population of patients survival was significantly higher in patients with a PS of 0-1 (P < 0.05). Patients with a PS of 0-1 and a resected tumor had the significantly longest survival both in EEP-L treated patients and in all evaluable patients in the two studies. The most frequent World Health Organization Grade 3-4 toxic effects were gastrointestinal in Study A and hematologic in Study B. No treatment-related death was observed.. The efficacy of 5-FU, modulated with 6S-LV, is moderate in patients with advanced gastric carcinoma, similar to cisplatin-containing regimens. PS and other prognostic factors could influence the response rate, which does not appear to be a reliable parameter for evaluating the outcome of chemotherapy trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Indazoles; Leucovorin; Male; Middle Aged; Prognosis; Quality of Life; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective response, with a median duration of 5 months. Median survival time for all patients was 8 months. In 16 of 36 patients (44%), treatment determined a significant relief of symptoms. Out-patient paclitaxel given over 3 h may be effective as salvage treatment in patients with advanced gastric cancer refractory to first line chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Time Factors

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Rate

On the basis of recent clinical data suggesting that high-dose continuous 5-fluorouracil (5-FU) is able to overcome resistance to 5-FU bolus application in gastric carcinoma, a phase II study was performed to evaluate the activity and toxicity of weekly high-dose 5-FU and leucovorin plus biweekly alternating doxorubicin and cisplatin as the first-line treatment in patients with advanced gastric carcinoma. Between October 1995 and September 1997, 24 consecutive patients with locally advanced (n=4) or metastatic (n=20) gastric carcinomas were treated with a combination of 500 mg/m2 leucovorin as a 2-h infusion, followed by 2.0 g/m2 5-FU as a 24-h continuous infusion once weekly for 6 weeks, plus 20 mg/m2 doxorubicin as a bolus application and 50 mg/m2 cisplatin as a 1-h infusion, week 1, 3 and 5 (FLAP regimen). Response, toxicity and survival data were evaluated. A total of 20 patients were evaluable for response and 24 for toxicity. Objective responses were observed in 11 patients (55%) with no complete remission. Four patients (20%) showed stabilization and 5 patients (25%) experienced progressive disease. The median time to disease progression was 8 months and the overall duration of survival was 14 months. Myelosuppression was significant. In 2 patients, grade 4 WHO thrombocytopenia and leukopenia/anaemia respectively were registered, but there were no treatment-related deaths. We conclude that the weekly alternating FLAP regimen is effective in advanced gastric carcinoma with tolerable toxicity. However, significant myelotoxicity and frequent hospitalization suggest that FLAP should not be preferred to other regimens used in metastatic disease. Currently we intend to establish this regimen in the neoadjuvant setting in patients with primary unresectable localized gastric carcinomas.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Female; Floxuridine; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Local extension prevents curative resection in more than two-thirds of gastric cancer patients. Unfortunately, resectability is one of the main prognostic factors in these patients, and survival is longer when tumours are completely removed. Preoperative chemotherapy is an attractive concept for obtaining curative resection. Thirty-two locally advanced unresectable gastric cancer patients were enrolled in five Italian Group for the Study of Digestive Tract Cancer (GISCAD) centres. For 16 patients, surgical unresectability was based on computerized tomography scan evaluation of tumour size (four patients) and invasion of adjacent structures (12 patients), whereas in another 16 patients locally advanced disease was confirmed by laparotomy. They received weekly administration of cisplatin 40 mg m(-2), 5-fluorouracil 500 mg m(-2), epidoxorubicin 35 mg m(-2), 6S-stereoisomer of leucovorin 250 mg m(-2) and glutathione 1.5 g m(-2). From the day after to the day before each chemotherapy administration, filgrastim was administered by subcutaneous injection at a dose of 5 microg kg(-1). One cycle of therapy consisted of eight weekly treatments. Fifteen of 32 patients (47%) responded to chemotherapy, whereas 13 (41 %) had stable disease and four (12%) progressed on therapy. Of the 15 responding patients, 13 were completely resected after chemotherapy and two of them had a complete pathological response. Two clinically responding patients were found unresectable at operation because of peritoneal seeding. At a median follow-up from the start of treatment of 24 months (range 11-39 months), 10 of 13 resected patients are alive and eight are relapse free. Three patients died after 11, 12, and 14 months respectively. Toxicity was acceptable: side-effects consisted mainly of grade II National Cancer Institute common toxicity criteria (NCICTC) leucopenia and thrombocytopenia in ten patients. Neither treatment-related death nor surgical complications in patients undergoing surgery were observed. This weekly intensive regimen enabled resection in half of previously inoperable tumours with a moderate toxicity. It can be offered to patients with locally advanced unresectable gastric cancer to obtain curative resection.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Filgrastim; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Recombinant Proteins; Stomach Neoplasms

Eleven patients with liver metastasis from gastric cancer were treated by intermittent arterial infusion using OK-432 and recombinant IL-2 in combination with anticancer drugs. The direct effects for liver metastasis were PR 3 (response rate 30%), MR 2, NC 3, PD 1 and NE 1. Papillary adenocarcinoma showed a highly effective rate. The mean survival period was 326 days and the 50% survival period was 318 days. Out of 4 patients who underwent surgical resection for metastatic liver tumor, one showed recurrence, and the other is now healthy without any sign of recurrence for 8 years after the operation. In 7 patients with liver metastasis from colorectal cancer, intermittent arterial infusion therapy using Leucovorin, CDDP and 5-FU was performed. The direct effects were CR 2, PR 1, MR 1, PD 2, NE 1; the mean survival period was 478 days, and the 50% survival period 556 days. Out of 8 patients who underwent liver resection for metastasis, all patients remained alive for 687 mean survival days without liver recurrence. No severe side effects were noted in either therapy.

Topics: Adenocarcinoma, Papillary; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Immunotherapy; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Interleukin-2; Leucovorin; Liver Neoplasms; Male; Middle Aged; Picibanil; Recombinant Proteins; Stomach Neoplasms

The efficacy of the treatment of advanced gastric cancer is not very good. The response rate to the original etoposide--leucovorin--5-fluorouracil (ELF) treatment is 53% with tolerable side effects. Whether increasing the dose intensity by prolonging the duration of infusion with 5-fluorouracil (5-FU) and leucovorin (LV) from 3 to 5 days for advanced or metastatic gastric cancer patients would enhance the efficacy but not increase side effects is still unknown.. Thirty-six advanced or metastatic gastric cancer and chemotherapy-naïve patients with measurable or evaluable diseases were scheduled to receive intravenous etoposide 100 mg/m2/day on days 2-4, LV 300 mg/m2/day intravenously and 5-FU 500 mg/m2/day intravenously on days 1-5, every 4 weeks. All patients who received at least two courses of chemotherapy were evaluated for tumor response, survival and response duration and toxicity according to the WHO criteria.. Thirteen patients showed a response, including five with complete response (CR). The overall response rate was 36% (95% confidence interval, CI, 20-52%) in the whole group and 46% (95% CI 28-66%) in the 28 patients with measurable disease. The median progression-free interval and overall median survival time were 5 and 7 months, respectively. The most frequent toxicity was alopecia (grade I/II 56.3%). The incidence of grade III or greater myelosuppression was 5.9%. No treatment-related death occurred.. The efficacy of the modified ELF by increasing the dosages of 5-FU and LV is not superior to the results of the original regimen, yet it is a relatively safe and tolerable combination regimen for advanced gastric cancer.

Topics: Adult; Aged; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Prognosis; Stomach Neoplasms; Survival Analysis

Topics: Antibiotics, Antineoplastic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Stomach Neoplasms; Treatment Outcome

The objective of this phase I-II study was to determine the efficacy and toxicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I study were as follows: methotrexate 50 mg/m2 intravenous bolus day 1; leucovorin 20 mg/m2 intravenous bolus days 2 through 4, starting 24 hours after the methotrexate dose; 5-fluorouracil 325 mg/m2 intravenous bolus 15 minutes after leucovorin days 2 through 4; doxorubicin 25 mg/m2 intravenous bolus day 8; and oral etoposide 50 mg/day for 14 days, starting on day 8. A new cycle started on day 28. A total of 42 patients were treated--10 patients in the phase I study and 32 patients in the phase II study. Dose-limiting toxicity was encountered in the phase I study on the second escalation step, when doxorubicin was escalated to 30 mg/m2 and 5-fluorouracil was escalated to 350 mg/m2. In the phase II study 28 patients (109 courses) were evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neutropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and grade 3 diarrhea was infrequent, documented in two patients (two courses) and three patients (four courses), respectively. All other toxicity was grade 1 and grade 2. The combined objective response rate in 38 evaluable patients entered in both studies was 23.3% (six partial responses and one complete response). Stable disease was documented in 15 patients (39.5%). The median survival for the 42 patients entered in both trials was 6.9 months (95% confidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the etoposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and methotrexate (FMTX) regimens in a recently reported, multicenter, phase III study.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Stomach Neoplasms; Survival Analysis

The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14 days. Based on the promising results obtained with this regimen in patients with advanced colorectal cancer, the Oncopaz group performed several phase II trials using this combination with other drugs to treat advanced gastric, lung, head and neck, and breast cancers. When combined with etoposide in gastric cancer, the regimen was shown to be active and well tolerated. However, when used with cisplatin to treat non-small cell lung cancer, a low response rate and high toxicity precluded its recommendation for further study. The addition of carboplatin in the treatment of head and neck cancer demonstrated moderate activity with low toxicity. In an ongoing trial of advanced breast cancer, preliminary results indicate that the combination of idarubicin, UFT, and leucovorin is active, with moderate, primarily hematologic toxicity. Trials of new combinations are warranted to take advantage of the pharmacokinetic properties and oral bioavailability of UFT and leucovorin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Etoposide; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Stomach Neoplasms; Tegafur; Uracil

The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.. Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.. More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).. The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Quality of Life; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Because only approximately 50% of gastric carcinomas are resectable for cure, the authors hypothesized that effective systemic preoperative (neoadjuvant) chemotherapy, aimed at decreasing the size and extent of the primary tumor and eradicating distant microscopic disease, may increase the rate of resectability and have a greater impact on survival than postoperative (adjuvant) treatment alone. In addition, because the peritoneal cavity is the most common site of first recurrence after successful gastric cancer resection, intraperitoneal (IP) chemotherapy seemed a logical choice for postoperative (adjuvant) treatment.. Fifty-nine patients with invasive primary gastric adenocarcinoma who were deemed resectable for cure entered a clinical trial that called for 2 cycles of protracted infusion 5-fluorouracil with weekly leucovorin and cisplatin chemotherapy followed by surgery. Approximately 3-4 weeks after potentially curative surgery, patients were scheduled to receive two cycles of IP 5-fluoro-2'deoxyuridine and cisplatin.. Of the 59 patients studied, 58 (98%) received both cycles of systemic chemotherapy. Fifty-six patients (95%) underwent surgery: 40 patients (71%) had resections intended to cure for Stage 0-IIIB disease, 15 patients (27%) had palliative surgery for Stage IV gastric carcinoma, and one patient died intraoperatively without being staged. Two patients refused surgery, and the remaining patient died of progressive disease prior to surgery. Thirty-one of the 40 patients who underwent curative surgery completed both cycles of postoperative IP therapy; 4 patients received only 1 cycle. Three patients (5%) died secondary to treatment complications. There were two operative deaths, and one patient died of peritonitis associated with Grade 4 granulocytopenia. Nine of the 40 patients (23%) whose carcinomas were resected for cure had recurrent carcinoma. With a median follow-up period now exceeding 45 months, the calculated median survival for the 59 patients entered into the trial is >4 years.. This program of preoperative systemic and postoperative IP chemotherapy has been found to be safe and appears to decrease gastric carcinoma recurrence rates and increase survival compared with historic controls.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Female; Floxuridine; Fluorouracil; Humans; Infusions, Intravenous; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Stomach Neoplasms; Tomography, X-Ray Computed

A Phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy (FLAP) in patients with previously untreated advanced gastric and gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients were enrolled to received FLAP in this multi-institutional trial. Response, toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated objective responses, with two complete responses (5%) and 13 partial responses (31%). The median time to disease progression was 17 weeks, and the overall survival duration was 30 weeks. Myelosuppression was significant, requiring dose modifications, but there were no treatment-related deaths. FLAP is an active regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We are presently using this regimen in the neoadjuvant setting in patients with gastric and GE junction cancers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Doxorubicin; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Treatment Outcome

A phase II trial was performed to evaluate the efficacy and toxicity of the combination of paclitaxel and 5-fluorouracil (5-FU)/folinic acid in patients with advanced gastric carcinoma. Twenty-two patients (six female and 16 male) with advanced or metastatic disease were enrolled. None of them had received prior chemotherapy. Paclitaxel was administrated as a 3 h infusion of 175 mg/m2 at days 1 and 22, 5-FU 2000 mg/m2 i.v. over 24 h and folinic acid 500 mg/m2 i.v. 2 h prior to 5-FU weekly from days 1 to 36. Seven patients (32%) had partial remissions including the lungs, skin, lymph nodes and locally advanced primary tumor. The median overall survival was 11 months (range 1-17+) and the median progression-free interval was 8 months (range 1-13+). Neutropenia (WHO grade III/IV) occurred in 14% of patients. Other main toxicities were alopecia in 45%, fever/infection in 9%, and nausea/vomiting and diarrhea in 5%. In conclusion, the combination of paclitaxel and continuously infused 5-FU/folinic acid appears to be an active regimen for advanced gastric carcinoma with a remission rate comparable to ELF or FAMtx. The moderate toxicity allows treatment on an outpatient basis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Outpatients; Paclitaxel; Stomach Neoplasms

Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined with etoposide and cisplatin (Platinol). This regimen resulted in a 39% response rate and high toxicity. Then we used the combination UFT (tegafur and uracil)/leucovorin/etoposide: UFT 390 mg/m2/day orally on days 1 to 14; leucovorin 500 mg/m2 i.v. day 1, and 15 mg/12 h orally on days 2 to 14; and etoposide 100 mg/m2 i.v. on day 1 and then 200 mg/m2/day orally on days 2 and 3. Forty-six patients received a median of five courses. Five patients (11%) achieved a complete response and 12 (26%) a partial response, for an overall response rate of 37%. The response rate was 50% in patients with an Eastern Cooperative Oncology Group performance status of 0 to 1. Grades 3 to 4 toxicities appeared as follow: 17% of patients had diarrhea, 11% had nausea/vomiting, and 13% of patients had anemia. One patient died of neutropenia and sepsis. The median survival time was 9 months. In summary, UFT/leucovorin/etoposide is effective and moderately toxic in patients with advanced gastric cancer. A new trial with UFT/leucovorin/epirubicin is ongoing.

Topics: Anemia; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Combinations; Etoposide; Female; Forecasting; Humans; Leucovorin; Male; Nausea; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided daily doses for 21 days followed by a 7-day rest period. The median age of the patients was 64 years, and the median World Health Organization performance status was 2. Patients received a median of two courses of treatment (range, 1 to 25). Among 37 evaluable patients, two patients achieved a complete response, and eight had partial responses, for an overall response rate of 27% (95% confidence interval, 15.4% to 42.9%). Stable disease was reported in 12 patients (32%) and another 15 showed disease progression. The median duration of response was 30 weeks, and the median duration of survival was also 30 weeks (range, 8 to 111). All patients were evaluable for toxicity. Significant toxicity (World Health Organization grade 3 or 4) included diarrhea in seven patients (18%), oral mucositis in six (15%), and nausea/vomiting in six patients. We conclude that oral UFT plus leucovorin, an outpatient regimen, has favorable activity in patients with gastric carcinoma and has tolerable toxicities.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

The current phase II study evaluates the safety and efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and 5-fluorouracil (5-FU) plus folinic acid in patients with advanced gastric cancer. Paclitaxel 175 mg/m2 was given intravenously over 3 hours on days 1 and 22; folinic acid 500 mg/m2 given intravenously over 2 hours followed by 5-FU 2,000 mg/m2 given intravenously over 24 hours was administered on days 1, 8, 15, 22, 29, and 36. Six weeks of treatment were considered one cycle, and each cycle was followed by 2 weeks off treatment. Twenty-two patients (six women and 16 men) with advanced/metastatic gastric cancer were entered on trial. All patients are evaluable for response and toxicity. None had received prior chemotherapy. Radiologically metastatic sites included gastric lymph nodes (64%), liver (36%), lungs (18%), peritoneum (18%), bone (9%), and skin (5%). No complete responses were observed. Seven patients (32%; 95% confidence interval, 12% to 52%) had a partial response. Sites of partial responses included the lungs, skin, lymph nodes, and locally advanced tumor. Twelve patients (55%) had stable disease and three (14%) had disease progression. At a median follow-up of 12 months (range, 1 to 17+ months), the median overall survival for all patients was 11 months (range, 1 to 17+ months; 95% confidence interval, 6.8 to 18.2) and the median progression-free interval was 8 months (range, 1 to 13+ months; 95% confidence interval, 4.7 to 9.8). Severe nonhematologic toxicities were alopecia (45%), fever/infection (9%), diarrhea (5%), and nausea/vomiting (5%). Grade 3/4 neutropenia occurred in three patients (14%). In summary, paclitaxel given every 3 weeks in combination with once-weekly, 24-hour continuous infusions of 5-FU/folinic acid is active in advanced gastric cancer and appears to achieve response rates comparable to regimens like etoposide/folinic acid/5-FU or 5-FU/doxorubicin/methotrexate. The toxicity of this new combination is moderate and allows treatment in an outpatient setting. Ongoing studies are evaluating the activity of paclitaxel combined with weekly continuous infusions of 5-FU/folinic acid with or without cisplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Paclitaxel; Stomach Neoplasms; Survival Rate; Treatment Outcome

After curative resection for gastric adenocarcinoma, 103 patients, all with positive nodes, were randomised so that 48 received adjuvant chemotherapy of epidoxorubicin (EPI) 75 mg m-2 on day 1, leucovorin (LV) 200 mg m-2 on days 1-3 and 5-fluorouracil (5-FU) 450 mg m-2 on days 1-3, every 21 days for 7 months, whereas the remaining 55 did not. During the first year of observation, 21 control patients (38%) and five treated patients had recurrences. After a follow-up period of 36 months, 12 of the treated patients (25%) and only seven controls (13%) were still alive. At that point, the median survival was 13.6 months for the 55 untreated patients and 20.4 months for the 48 treated patients, a significant difference. We found a survival advantage for patients treated with the EPI-LV-5-FU regimen and a consistent delay in the appearance of recurrent or metastatic cancer. Acute toxicity was mild and treatment was well accepted by all patients. There was no long-term toxicity or any cardiac toxicity. We conclude that this particular chemotherapy, administered shortly after gastric resection, improves survival rate in node-positive gastric cancer patients, even although final assessment of this particular adjuvant approach must await completion of the trial.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Epirubicin; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Neoplasm Staging; Proportional Hazards Models; Recurrence; Stomach Neoplasms; Survival Rate; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Sensitivity and Specificity; Stomach Neoplasms

A phase II trial was performed with oral UFT plus leucovorin (LV) in 16 patients with advanced gastric carcinoma. Treatment consisted of UFT, 480 mg/m(2)/day, in conjunction with LV administered at 25 mg/m(2)/day per os in divided daily doses for 21 days followed by a 7-day rest period. The median age of patients was 64 years, with a median World Health Organization (WHO) performance status of 2. One patient was previously treated with etoposide, doxorubicin, and cisplatin (EAP). A median of four courses of treatment were given per patient (range: 1-9). Among 14 evaluable patients, one patient achieved a complete response and 3 had partial responses (response rate: 28.5%, 95% confidence interval, 4.9 to 52.3%). Stable disease was reported in 5 patients (35.7%) and another 5 showed progression. The time to progression was 17, 18, 27, and 76+ weeks for the responding patients, respectively. The median duration of survival was 25 weeks (range: 10-76+) for 14 evaluable patients. All patients were evaluable for toxicity. The main toxicity was diarrhea and oral mucositis. Significant toxicity (WHO grade 3 or 4) included diarrhea in 7 patients (43.8%), oral mucositis in 2 (12.5%), and nausea/vomiting in 2, respectively. We conclude that oral UFT plus LV, an out-patient regimen, has favorable activity in gastric carcinoma patients and has tolerable toxicities.

Topics: Administration, Oral; Adult; Aged; Antibiotics, Antineoplastic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Diarrhea; Disease Progression; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Stomatitis; Survival Rate; Tegafur; Vomiting

The efficacy and toxicity of a combination of etoposide 100 mg/m2/day iv on day 2-4, leucovorin 300 mg/m2/day iv, and 5-FU 500 mg/m2 day iv on day 1-5 every 4 weeks were assessed in 21 patients with advanced gastric cancer with measurable or evaluable diseases. Eight patients had an objective response, including 3 in CR. The overall response rate was 38.1% (95% CI 33.4-42.8%). Five of 8 patients who exhibited locally advanced and unresectable diseases had an objective response (2 CR, 3 PR). The response rate in patients with metastatic disease was 23.0% (95% CI 14.4-31.6%). The median progression-free interval and overall survival time were 7 and 10 months, respectively. The most frequent side effect was alopecia (Gr I/II 71.4%). No treatment-related death occurred. Modified ELF is a relatively effective and tolerable combination regimen for advanced gastric cancer and can be safely administered to elderly patients and patients with systemic diseases.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Both the biochemical modulation and the continuous administration of 5-fluorouracil (5-FU) have achieved promising results in patients with gastric carcinoma. Conversely, several studies on gastric carcinoma have demonstrated that the combination of etoposide (VP-16), leucovorin (LV), and 5-FU (ELF) is efficacious and moderately toxic. UFT is a combination of uracil and tegafur (ftorafur) in a 4:1 molar ratio. It can be administered orally for several weeks, thus stimulating the effects of a continuous infusion of 5-FU. Its combination with LV increased the efficacy of UFT. We conducted a Phase II study on patients with gastric carcinoma using the combination VP-16-LV-UFT. This combination is administered mainly orally (p.o) and could yield a good response rate and low toxicity.. Forty-six patients with bidimensionally measurable disease were entered into the study. Patients received VP-16 100 mg/m2 IV on Day 1 and 200 mg/ m2 p.o. on Days 2 and 3; LV 500 mg/m2 administered intravenously (i.v.) on Day 1, followed by p.o. LV 15 mg every twelve hours on Days 2 to 14. Patients also received UFT p.o. 390 mg/m2/day on Days 1 to 14. Treatment was repeated every 28 days for a minimum of 3 courses per patient. All courses were given on an outpatient basis.. Four patients (9%) had a complete response, and 12 a partial response (26%) for an overall response rate of 35% (95% confidence interval: 22-51%). The median duration of response was 10 months. The median overall survival was 9 months. The main side effects were gastrointestinal. Grade 3 to 4 toxicity was encountered as follows: diarrhea in 17% of the patients, nausea/vomiting in 11%, anemia in 13%, mucositis and leukopenia in 4% each, and thrombocytopenia in 2%. One patient died of sepsis and neutropenia.. VP-16-LV-UFT has an activity comparable to that of other schemes and a low incidence of side effects. Furthermore, since it is administered mainly orally, hospitalization is avoided, which makes this scheme suitable for patients with advanced gastric carcinoma.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Anemia; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diarrhea; Drug Administration Schedule; Etoposide; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Middle Aged; Nausea; Remission Induction; Stomach Neoplasms; Survival Rate; Tegafur; Vomiting

It was our intention to verify if increases of granulocyte colony stimulating factor (G-CSF) dose were able to reduce treatment delays due to leukopenia in our weekly regimen of cisplatin (40 mg/m2), epidoxorubicin (35 mg/m2), 6S-leucovorin (250 mg/m2) and 5-fluorouracil (500 mg/m2), usually supported by G-CSF at a dose of 5 mu g/kg. Forty five patients with advanced gastric carcinoma (30 males and 15 females; median age 64 years) were randomized to receive three different doses of G-CSF (5, 8 and 10 mu g/kg) by s.c. injection. We did not observe any difference in the mean value of neutrophil counts at each of the 8 weeks of treatment; while we registered a higher incidence of severe neutropenia (< 500/mm3) in patients receiving higher G-CSF doses: two patients in the group at 5 mu g/kg, four in the group at 8 mu g/kg and seven in the group at 10 mu g/kg. Furthermore, low doses of G-CSF allowed a similar number of chemotherapeutic administrations in the eight study weeks. The results arising from our study do not seem to support the use of higher doses of G-CSF, at least in not such a weekly regimen.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

5-Fluorouracil (5-FU) remains a standard therapy for patients with advanced gastric cancer. There has been no study using an oral regimen with a combination of tegafur, a masked compound of 5-FU, and leucovorin in gastric cancer. The purpose of this study was to determine whether orally administered low-dose leucovorin enhances thymidylate synthase (TS) inhibition when added to tegafur-uracil (UFT) in patients with gastric cancer.. A group of 26 patients with resectable gastric cancer were assigned to one of two regimens: UFT alone or UFT plus leucovorin. UFT, equivalent to 400 mg/day tegafur, with or without 30 mg/day leucovorin, was administered orally in divided daily doses every 12 h for 3 consecutive days prior to surgery. Tumor specimens were taken immediately following gastrectomy, and the TS inhibition rate (TSIR) was determined using a ligand-binding assay.. The TSIR was significantly higher in the UFT plus leucovorin group than in the UFT alone group (P < 0.01). The TSIR in the patients treated with UFT alone ranged between 14% and 50%, while six of the eight patients treated with UFT plus leucovorin had a TSIR of 55% or higher. The remaining two patients in the group treated with UFT plus leucovorin, with a TSIR of 31% and 44%, had undifferentiated tumors.. Our results suggest that orally administered low-dose leucovorin can add to the efficacy of UFT in patients with gastric cancer, and provide preliminary data for a randomized clinical trial.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Leucovorin; Male; Neoplasm Staging; Prospective Studies; Stomach Neoplasms; Tegafur; Thymidylate Synthase; Uracil

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Rate

The biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) has demonstrated significantly increased response rates in comparison with the use of 5-FU alone in patients with advanced colorectal carcinoma. However, the higher response rate of LV/5-FU may occur at the expense of increased toxicity and side effects such as diarrhea, myelosuppression, and mucositis. During chemotherapy, a high incidence of hypocalcemia associated with this chemotherapy regimen was noted. This study was therefore aimed at assessing the side effects of chemotherapy using low dose LV/5-FU on calcium metabolism.. Twenty-five patients with advanced gastric or colorectal carcinoma were treated with chemotherapy comprised of low dose LV administered at 20 mg/m2/ day by intravenous bolus, followed by 1-hour intravenous infusion of 5-FU at 425-600 mg/m2/day for 5 consecutive days every 28 days.. The toxic effects were generally mild, and included diarrhea, mucositis, leukopenia, and nausea/vomiting. Fifteen patients (65%) experienced hypocalcemia. The plasma 1,25-(OH)2D3 levels were significantly reduced on Day 5 due to the chemotherapy.. The toxic effects of the regimen were generally mild. However, a high percentage of hypocalcemia occurred with the combination of LV/5-FU. It is therefore necessary to examine carefully the serum calcium levels of patients when using this chemotherapeutic modality.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Calcium; Colorectal Neoplasms; Female; Fluorouracil; Humans; Hypocalcemia; Leucovorin; Male; Middle Aged; Parathyroid Hormone; Stomach Neoplasms

Etoposide, leucovorin and 5-fluorouracil (ELF) chemotherapy has been reported to be less toxic yet effective (response rates of 50%) in patients with advanced gastric cancer. A phase II study of ELF in 25 patients (11 males, 14 females, median age 53 years) with advanced adenocarcinoma of the stomach is reported. Patients received outpatient intravenous etoposide 120mg/m2 over 2 hours, folinic acid 300 mg/m2 over 2 hours, 5-fluorouracil 500 mg/m2 boluses daily for 3 days every 21 days. Of 17 measurable patients, there was one complete response (CR), 4 partial responses (PR) for a total response rate of 29.4%. Non-hematologic toxicity was modest (grade 0 vomiting 11/21, stomatitis 16/21, diarrhea 17/21). Grade 3/4 neutropenia was seen in 14/23, thrombocytopenia in 2/23, anemia in 5/23 patients. Median progression-free and overall survival was 4.1 and 7.1 months, respectively. In conclusion, ELF chemotherapy shows only modest activity in patients with advanced gastric cancer and is associated with severe hematologic toxicity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Hematologic Diseases; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Survival Rate

Previous trials in patients with colorectal carcinoma have indicated that enhancement of 5-fluorouracil (5-FU) by leucovorin (LV) can result in an improved response rate and increased survival.. Phase II trials were performed with patients who had either gastric or papcreatic adenocarcinoma with inetastases. Forty-one gastric carcinoma patients and 31 pancreatic carcinoma patients with measurable disease were treated with 5-FU, 425 mg/m2 intraveneosly (i.v.) on Days 1-5 plus LV, 20 mg/m2 i.v., on Days 1-5, reported at 4 and 8 weeks, and then every 5 weeks thereafter.. The patients with metastatic gastric carcinoma had a median survival of 4.8 months. There was a 22% objective response rate, including a 4.9% complete response rate and a 17.1% partial response rate. Among the 31 patients with pancreatic carcinoma, there was a median survival of 5.7 months. No patients in this group showed a response.. The response rate for patients with metastatic gastric adenocarcinoma was modest and this regimen may provide temporary palliation for some patients. However, 5-FU and LV treatment is ineffective against metastatic pancreatic carcinoma.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pancreatic Neoplasms; Stomach Neoplasms

The modulation of 5-fluorouracil (5-FU) with folinic acid (leucovorin, LV) is more efficacious than 5-FU alone in the treatment of metastatic colorectal cancer, and the combination of 5-FU with cisplatin is currently one of the most active regimens in advanced gastric cancer. A phase II study was therefore conducted to test the efficacy and toxicity of the combination of 5-FU, LV and cisplatin (FLP) in metastatic gastric cancer. 28 patients entered the study. Metastatic sites were observed in the liver (in 21 patients), the peritoneum (in 8), the lymph nodes (in 7) or the bones (in 1) and a local recurrence was noted in 4 cases. The performance status (using World Health Organisation criteria) was 0 for 13 patients and 1 or 2 for the others. Cycles of treatment were administered every 28 days and consisted of LV 200 mg/m2/day for 5 days followed by 5-FU 400 mg/m2/day for 5 days with cisplatin 100 mg/m2 on day 2. The response rate for the 27 evaluable patients was 51.8% (95% confidence interval (CI), 33-70.6%). There were four complete responses (14.8%) and 10 partial responses (37%). Median survival was 11 months and 4 patients were alive at 2 years. Both response rate and survival were better for patients with a good performance status. The overall toxicity was very low, except for 1 patient who died of dehydration and cardiac failure. In conclusion, the FLP protocol was effective and well tolerated in patients with metastatic gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Prospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Based on preclinical data and the promising results being achieved with infusional 5-FU in colorectal and breast cancer, we investigated a weekly schedule of a 24-hour infusion of 5-FU plus folinic acid (HD-FU/FA) in patients failing to first-line chemotherapy and HD-FU/FA plus cisplatin (C) or plus cisplatin/epidoxorubicin (C/E) in chemo-naive patients with advanced gastric cancer. In all three trials the results achieved with the tested chemotherapy regimens indicated high activity and good tolerability. All three protocols were administered as outpatient treatment. With HD-FU/FA and overall response rate of 24% and a median survival time of 5 months was observed in 17 patients refractory to or relapsing after first-line chemotherapy. HD-FU/FA/C induced an overall response rate of 66% and a median survival time of 13 months. Of note was the high activity of this regimen in patients with malignant ascites. HD-FU/FA/C/E also proved to be an interesting regimen similar active as HD-FU/FA/C but it was subjectively less well tolerated. In patients with locally advanced disease the response rate was 90% (10/11), and in patients with distant metastases 50% (8/16).

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Treatment Outcome

To improve the therapeutic ratio of palliative chemotherapy in patients with metastatic colorectal and gastric cancer 5-fluorouracil (5-FU) was administered as weekly high-dose 24-hour continuous infusion in combination with leucovorin (LV) and interferon-alpha-2b (IFN) as biomodulating agents: Chemotherapy consisted of a weekly schedule of 500 mg/m2 leucovorin as a 2-hour infusion, followed by a 24-hour continuous infusion of 2500 mg/m2 5-FU. IFN was administered subcutaneously at a dose of 3 mio I.E. three times a week. In patients with gastric carcinoma, etoposide (VP) 100 mg/m2 as 30-minute bolus infusion was added. Eighty-five patients (colorectal: 55 points, gastric: 30 points) are evaluable for response, toxicity, and survival analysis. Colorectal: CP+PR: 19/55 (34.5%), NC: 25/55 (45.5%), PD: 11/55 (20.0%). Median duration of remission in months (90% confidence interval): 5.2 (3.1 to 9.2), median survival since the start of salvage chemotherapy: 13.9 months (12.3 to 20.1), from initial diagnosis of metastasis: 30.2 months (26.3 to 44.5). Gastric: CR: 8/30 (26.7%), PR: 14/30 (46.6), NC: 5/30 (16.7), PD: 3/30 (10.0%). Median duration of remission in months (90% confidence interval): 6.75 (1.5 to 16.2), median survival since start of chemotherapy: 15.1 months (90% confidence interval 11.8 to 20.3 months). Hematologic toxicity: hemoglobin: I: 20.0%, II: 10.0%, leukocytes: I: 13.3%, II: 33.3%, III: 16.6%, platelets: I: 10.0% and III: 3.3%. Hematologic toxicity was moderate to negligible, peripheral toxicity consisted mainly of tolerable stomatitis and diarrhea. Dose and schedule intensified weekly 5-FU combination therapy in metastatic colorectal and gastric cancer is highly active in terms of response and median survival time. Chemotherapy pretreated patients with colorectal cancer seem to have a substantial survival benefit with this salvage protocol.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Dose-Response Relationship, Drug; Etoposide; Female; Fluorouracil; Humans; Infusions, Intravenous; Interferon-alpha; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Rate; Treatment Outcome

Based on encouraging treatment results with FU/FA or FU/IFN in gastrointestinal tract cancer, a phase II study was conducted to evaluate the effects and toxicity of combination FU/FA/IFN in patients (pts) with inoperable/metastatic gastric cancer.. IFN 6 M.U. s.c. 1 x/week, FU 500 mg/m2 bolus i.v. 1 x/week and FA 500 mg/m2 1 x/week as a 2-hour infusion. Of 72 treated pts, 72 (22 females, 50 males) are evaluable for response and toxicity. Median age was 55.6 years (28-80), and median Karnofsky performance status was 80% (70-100). Sites of measurable disease were inoperable primary tumors/local recurrence (18), liver metastasis (22), lymph nodes (31) and peritoneum (20). One pt had bone marrow metastasis and another had paraneoplastic hyperfibrinolytic coagulopathy.. 10/72 pts had complete response, 20/72 pts partial response, 40/72 pts tumor stabilization and 2/72 pts progressive disease. The median duration of response (CR/PR) was 9 months, the median progression-free interval 6 months, the median survival time was 9 months, and for responding patients (CR/PR) 12.5 months.. 1/72 pts had WHO grade 4 toxicity (diarrhea), 5/72 pts had WHO grade 3 toxicity (nausea 1, diarrhea 4). Except for 1 treatment-limiting grade 4 toxicity, no modifications of dose or schedule due to toxicity were required. Thirty-six of 44 pts experienced a significant reduction in tumor-related pain under treatment.. Biochemical modulation of FU with FA and IFN is effective in advanced gastric cancer. Moderate toxicity, outpatient treatment setting and high rates of amelioration tumor-related pain contribute to an effective palliation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Pain Management; Palliative Care; Quality of Life; Recombinant Proteins; Remission Induction; Stomach Neoplasms; Survival Analysis; Treatment Outcome

A randomized early phase II study using l-leucovorin (l-LV) and 5-fluorouracil (5-FU) against gastric cancer and colorectal cancer was conducted on a multi-institutional basis in Japan. The administration schedules: Arm A was 250 mg/m2 of l-LV and 600mg/m2 of 5-FU weekly, arm B was 100mg/m2 of l-LV and 370mg/m2 of 5-FU for 5 consecutive days, and arm C was 10mg/m2 of l-LV and 370mg/m2 of 5-FU for 5 consecutive days. In gastric cancer, the response rates were 35.7% (10/28) in arm A, 25% (7/28) in arm B and 0% (0/17) in arm C. On the other hand, in colorectal cancer, 32.4% (12/37) in arm A, 20% (8/40) in arm B and 11.1% (4/36) in arm C. Then, late phase II study using arm A was conducted for both gastric cancer and colorectal cancer. The response rate was 32.8% (21/64) in gastric cancer and now going in colorectal cancer. The combination of high dose l-LV and 5-FU seemed effective for advanced gastric cancer and colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Stomach Neoplasms

A phase II study was performed to assess the efficacy and toxicity of the combination of 5-fluorouracil (5-FU), leucovorin (LV), etoposide, and cisplatin (FLEP) in patients with advanced gastric carcinoma. A total of 46 consecutive, previously untreated patients with unresectable, measurable gastric carcinoma were treated with 300 mg/m2 LV, 100 mg/m2 etoposide, 500 mg/m2 5-FU, and 30 mg/m2 cisplatin on days 1-3 every 28 days. All courses were given on an outpatient basis. A total of 169 courses of treatment were given. In all, 18 of the 46 patients (39%) had an objective response [95% confidence interval (CI), 25%-54%] and 2 (4%) patients experienced a clinical complete response. The median duration of response was 5 months. The main side effects were hematological and gastrointestinal. Grade 3-4 toxicity was encountered as follows: leukopenia, in 9.5% of the courses; anemia, in 3%; thrombocytopenia, in 3%; nausea/vomiting, in 4%; and diarrhea, in 5%. Hospitalization due to fever and granulocytopenia was required in 5 patients, 3 of whom died of sepsis. In conclusion, FLEP shows moderate activity in patients with advanced gastric carcinoma, albeit at the cost of a high degree of toxicity. For this reason we do not recommend its use.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Stomach Neoplasms; Survival Rate

A multicenter cooperative study was conducted to evaluate the clinical efficacy of l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 69 cases of advanced gastric cancer. l-LV was administered intravenously by a 2-hour infusion at a dosage of 250 mg/m2 and 5-FU at a dosage of 600 mg/m2, intravenously via bolus one hour after administration of l-LV had been started. The combination was given weekly for 6 weeks followed by a 2-week rest period. Patients were evaluated for response after the sixth dose. Nineteen PRs were noted in the 55 patients for an overall response rate of 34.5%. Median survival time was 190 days for eligible cases, and 448 days for PR cases. Age and performance status (PS) appeared to influence clinical response. Patients aged 49 years or younger showed a significantly higher PR rate than those aged 50 years or older. The PR rate was significantly higher in the patients of PS 0-1 than those of PS 2. Diarrhea and leukopenia were experienced in 46.7% and 65% of patients, respectively. Patients who had severe toxicities required discontinuity of treatment. After recovery, treatment was repeated. The clinical results are promising for patients with advanced gastric cancer, particularly middle-aged patients. However, whether the l-leucovorin and 5-FU combination therapy will ultimately produce superior results in middle-aged patients awaits the results of Phase III trials.

Topics: Adult; Aged; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Survival Rate

A randomized early phase II study using l-leucovorin (l-LV) and 5-fluorouracil (5-FU) in gastric cancer was conducted. The administration schedules: Arm A was 250 mg/m2 of l-LV and 600 mg/m2 of 5-FU weekly, arm B was 100 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days, and arm C was 10 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days. PR was obtained in 10/28 (35.7%) of arm A, 7/28 (25.0%) of arm B and 0/17 (0%) of arm C, in complete cases. In eligible cases, 30.3%, 21.9% and 0%, respectively. Because there was no responder in arm C, the entry to arm C was stopped by controller at the point where 17 patients were treated with arm C. Median survival time was 9.6 months in arm A, 8.0 months in arm B and 5.9 months in arm C. Major toxicities were stomatitis, diarrhea and neutropenia. Stomatitis was seen more in arm B and C than in arm A. These data suggest that the high dose of l-LV and 5-FU seems to be a very promising combination, but there was no responder using low-dose l-LV schedule against gastric cancer. We thus selected arm A for the next late phase II study against gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neutropenia; Stomach Neoplasms; Stomatitis; Survival Rate

A total of 71 patients with advanced gastric carcinoma were randomized to receive either folinic acid + fluorouracil (arm A) or the same combination with the addition of 4-epidoxorubicin (arm B). Of the 62 evaluable patients (31 in both arms), six patients achieved a CR (10%) and 16 a PR (25.5%) with an overall response rate of 35.5% (29% in arm A and 42% in arm B; p = .28). Median duration of response was 6 and 7 months for arm A and B, respectively (p = .6). Responder patients showed a significantly better median survival duration than nonresponders (p = .01); in arm B the median survival duration was 16 months for responder patients in contrast to 7 months for nonresponders (p = .004). Toxicity was mild without significant differences between the two groups. There was one death due to hematological toxicity (arm A). The EPI-FA-FU combination appears effective and well tolerated with the additional advantage of being able to be administered in the outpatient clinic.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Epirubicin; Female; Fluorouracil; Humans; Italy; Leucovorin; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Survival Rate

The best schedule for administering floxuridine (FUDR) has not yet been established. Duration of infusion, need (and dosage) of leucovorin (folinic acid, FA), and circadian timing need to be further specified. Nevertheless, FUDR delivery according to circadian rhythms has allowed increase of dose intensity without enhancing the side effects. A 5-day infusional schedule combining FUDR and L-FA was devised as an attempt to increase dose intensity and to provide therapy every 3 weeks to patients with advanced cancer. An ambulatory programmable-in-time pump was used for this purpose. Fourteen patients entered this trial. Two dose levels (mg/kg x 5 days) were evaluated: 0.5 mg/kg/day in six patients and 0.525 mg/kg/day in eight patients. Both patient groups received a concurrent infusion of L-FA 10 mg/m2/day i.v. The delivery patterns of both FUDR and L-FA varied sinusoidally during the 24 hours with a maximum at 18.00 hours. Courses were repeated every 3 weeks. Of 35 courses, treatment produced mucosites greater than grade 2 in only two of them. No severe diarrhea, the dose-limiting toxicity of FUDR when infused over 14 days, was encountered at the dose levels tested. This 5-day chronotherapy schedule allowed delivery of a larger amount of FUDR than the flat delivery described in a previous report. A daily dose of 0.525 mg/kg FUDR, combined with 10 mg/mg2 L-FA, with intraindividual dose escalation according to tolerance, is recommended for future investigations of the activity of this chronotherapy schedule.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Carcinoma, Renal Cell; Chronobiology Phenomena; Colorectal Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Floxuridine; Humans; Infusions, Intravenous; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Neoplasms; Stomach Neoplasms

The prognosis in gastric cancer has been almost unchanged for the last 20 years. At the time of diagnosis the majority of patients have disseminated disease. The 5-year survival is only about 15%. Several efforts with numerous antineoplastic regimens have been studied. The most widely used regimen has been the FAM (5-fluorouracil, adriamycin, mitomycin C) regimen. Because of the cardiotoxicity and dose intensity of the FAM regimen, a low toxicity regimen, the ELF (etoposide, leucovorin, 5-fluorouracil) regimen, has been introduced. We present the data from the treatment of 26 patients (17 FAM, 9 ELF) with advanced gastric cancer at the University Hospital of Tromsø. The monthly costs of FAM and ELF treatment were calculated to a price of 553 pounds and 2976 pounds (British pounds). The median survival of 5 months (FAM) and 6 months (ELF) is in accordance with other studies. Assuming that the median survival in our study is correct, the cost of one year saved was 123,834 pounds, while the cost of one QALY (quality adjusted life year) employing the ELF compared to the FAM regimen was 104,334 pounds. We conclude that the standard ELF regimen too expensive in the treatment of gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Doxorubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Mitomycin; Stomach Neoplasms

The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folate folinic acid (FA) in the treatment of patients with advanced gastric cancer was examined.. The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5).. There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency.. Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Antidotes; Antimetabolites, Antineoplastic; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Stomach Neoplasms; Survival Rate

The main purpose of this trial was to investigate the activity of a less toxic regimen in patients with advanced gastric carcinoma regarding response rate and survival. We report on a pilot study of 20 patients treated with the combination of 5-fluorouracil and folinic acid. 5-fluorouracil was administered at a daily dose of 450 mg/m2 followed by folinic acid 200 mg/m2 for four consecutive days every four weeks. The overall response rate was 15% with one complete and two partial responders. The median duration of response was 11, 10 and 10 months respectively. The median survival of all patients was 9 months. Toxicity was mild and consisted primarily of diarrhea. Stomatitis and myelosuppression occurred rarely. In conclusion, the combination of 5-fluorouracil and folinic acid has moderate activity in gastric cancer, while median survival appears similar to the other more intensive regimens. The combination is very well tolerated with minimal toxicity. A detailed review of the literature regarding the effectiveness of the above regimens on response rate, overall survival and toxicity is also presented.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Stomach Neoplasms

A weekly schedule of a 24-h high-dose 5-FU infusion in combination with folinic acid was investigated as salvage therapy in patients with advanced gastric cancer.. Seventeen patients with progressive disease after chemotherapy were treated with a weekly schedule of 500 mg folinic acid/sqm by i.v. 2-h infusion followed by an i.v. 24-h infusion of 2.6 g 5-FU/sqm times six. Fourteen of the 17 patients (82%) had been pretreated in regimens which included 5-FU/folinic acid i.v. bolus.. Toxicity was mild, with diarrhea, mucositis and nausea; WHO grade III/IV diarrhea was observed in only two patients. Three patients achieved partial remissions (18%; 95% confidence interval: 0%-38%) and 7 patients stable disease (41%; 95% confidence interval: 17%-64%). Their median survival time was five months (range 1.5-10 months) after the onset of salvage therapy.. This schedule of weekly 24-h infusions of high-dose 5-FU and folinic acid is effective, even in patients pretreated with or resistant to regimens including 5-FU/folinic acid i.v. bolus. Based on these data, it appears that this schedule of high-dose 5-FU/folinic acid in first-line combination chemotherapy merits investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Remission Induction; Salvage Therapy; Stomach Neoplasms; Survival Rate

The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients.. One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses.. The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable.. This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Prospective Studies; Remission Induction; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Because the ELF regimen (etoposide, leucovorin and 5-FU) in advanced gastric cancer was recently advocated as an active, non-toxic schedule, and drug scheduling of etoposide proved to be important, we performed a pilot study using the original ELF regimen (A), followed by a phase II study of a modified ELF schedule (B) using oral etoposide.. Of the 40 patients entered in the consecutive trials 15 were treated according to the original ELF (A) and 25 according to the modified ELF regimen (B). The primary tumor was originally in the stomach in 22 and the oesophago-cardiac junction in 18. In 6 there was locally advanced and in 34 metastatic disease.. Toxicity was mild in ELF (A): grade III leukopenia in 6/63 cycles. The ELF (B) caused slightly more myelosuppression: grade III leukopenia in 4/102 and grade IV in 2/102 cycles, resulting in septicaemia in two patients, and toxic death in one. No severe thrombocytopenia was seen. Hemorrhage (4 cases) was exclusively related to tumor progression. Response rates were 7% (0%-21%) and 28% (10%-46%) for ELF (A) and ELF (B), respectively. Subjective response, however, leading to a clinically significant decrease of dysphagia and pain, was seen in 53% and 56% of the patients.. The modified ELF regimen (B) can be applied safely on an out-patient basis, and shows moderate activity in advanced gastric cancer which leads to an improved quality of life.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Pilot Projects; Stomach Neoplasms

A total of 23 advanced gastric cancer patients older than 65 years received 500 mg/m2 5-fluorouracil i.v. on days 2-4, 120 mg/m2 vepesid i.v. on days 2-4, 150 mg/m2 6S-leucovorin on days 2-4, and 5 MU/m2 interferon alpha-2b on days 1-5, with cycles being repeated every 3 weeks. Toxicity was severe at an interferon (IFN) dose of 5 MU/m2; only one patient tolerated this dose. In 18 patients an IFN dose of 3 MU/m2 and in 3 other patients a dose of 4 MU/m2 could be given without producing toxicity. At an IFN dose of 5 MU/m2 the most common toxicities encountered were stomatitis (grade 4 in 1 patient and grade 3 in 12 patients), leukopenia (grade 4 in 1 patient and grade 3 in 5 patients), and thrombocytopenia (grade 3 in 3 patients). Two patients achieved a complete response and eight showed a partial response, resulting in an overall response rate of 45% [95% confidence interval (CI), 25%-64%]. The median survival was 7 months for all patients and 9 months for responding patients. In conclusion, without substantially increasing the toxicity, IFN can be added to the etoposide/leucovorin/5-fluorouracil combination, at a dose of 3 MU/m2. To verify the possible enhancement by IFN of the activity of this combination, a randomized trial is under way.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Levoleucovorin; Male; Pilot Projects; Recombinant Proteins; Stomach Neoplasms

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biological Availability; Etoposide; Fluorouracil; Gastrectomy; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Stomach Neoplasms

The study was performed to assess the toxicity and impact on relapse pattern of postoperative intraperitoneal cisplatin, 5-fluorouracil, leucovorin and interferon therapy as adjuvant treatment for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2 N1-2; T3-4 N any Mo).. Starting 14 to 21 days after potentially curative resection of primary gastric cancers, 22 patients were given intraperitoneal cisplatin, 60 mg/m2; 5-fluorouracil, 1000 mg/m2; 6S-leucovorin, 250 mg/m2; interferon alpha 2b, 10 MU/m2; every other week for six times.. After a median follow-up of 24 months, 63% of patients were alive and free of disease. Eight patients had recurred; five had an intraabdominal component, and 3 had extraabdominal failure. Toxicity was mild: no grade III-IV WHO toxicity was observed.. Intraperitoneal cisplatin, 5-fluorouracil, 6S-leucovorin and interferon is a tolerable therapy in the postoperative setting for patients with resected gastric cancer. These data make this approach interesting for the development of new programs of adjuvant therapy of high-risk gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Injections, Intraperitoneal; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Stomach Neoplasms; Survival Rate

Metastatic disease is a common problem in gastric cancer and the development of better chemotherapeutic regimens is a clear priority in gastrointestinal oncology.. Ninety consecutive, previously untreated patients with unresectable or measurable metastatic gastric cancer were included in a multicenter phase II trial with a combination of folinic acid (200 mg/m2) and 5-fluorouracil (400 mg/m2) days 1-3, with epidoxorubicin (60 mg/m2) and cisplatin (100 mg/m2) on day 2.. A total of 376 courses of FLEP were given, with a median of four courses per patient. Objective responses were observed in 32 (35%) patients (CI at 95%: 25.7%-46.3%). Eight (9%) patients experienced clinical complete remissions. Median time to progression was 25 weeks for the entire group of patients and 38 weeks for responders. Myelosuppression was the primary toxicity. WHO grade 3 leukopenia appeared in 26 patients (29%). Ten presented episodes of febrile neutropenia requiring hospitalization, but no toxic deaths were observed. Grades 3 and 4 thrombocytopenia were seen in 8 and 1 patients, respectively. Median survival time was 8 months for all treated patients and 11 months for responders.. The FLEP regimen is an active combination in advanced gastric cancer with moderate toxicity that warrants further testing in a phase III trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

We conducted a multicentric phase II study on advanced gastric cancer to determine the efficacy and toxicity of treatment with epidoxorubicin (EPI) plus high doses of leucovorin (LV) and 5-fluorouracil (5-FU). Thirty-seven patients with measurable disease were enrolled into the trial and treated with EPI 75 mg/m2 on day 1 and LV 200 mg/m2 plus 5-FU 450 mg/m2 from day 1 to 3, the cycle being repeated every 3-4 weeks from a median of five cycles per patients. The response rate was 49% in 35 evaluable patients, with two complete remissions and 15 partial responses. Median response duration was 12.4 months; median survival for responding patients was 17.3 months, which was significantly longer than 8.7 months for non-responding patients. General toxicity was usually mild, myelotoxicity was moderate and there was no evidence of cardiac toxicity. These results show that EPI-LV-5-FU is an effective regimen for advanced gastric carcinoma. The efficacy of this combination should now be tested as an adjuvant therapy in resectable gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Interactions; Epirubicin; Female; Fluorouracil; Humans; Infant, Newborn; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Esophageal Neoplasms; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Middle Aged; Stomach Neoplasms

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms

To determine the maximum tolerated dose of epirubicin for use in combination with 5-fluorouracil (5-FU) and low-dose leucovorin (LV), a Phase I-II trial was conducted in 37 patients with advanced gastric carcinoma.. The doses of 5-FU (425 mg/m2) and LV (20 mg/m2), both given intravenously on days 1-5, were held constant while the dose of epirubicin was escalated in cohorts of patients (beginning dose, 50 mg/m2 on day 1). Cycles were repeated every 4 weeks.. Significant gastrointestinal symptoms and myelosuppression were observed infrequently at the initial dose level. At a dose of 60 mg/m2 of epirubicin on day 1, however, five of eight patients had significant mucosal toxic effects during the first cycle of therapy. In addition, two patients treated at this dose level had Grade 4 granulocytopenia with insufficient recovery to permit a second course by day 28, and one patient each had severe diarrhea and nausea and vomiting. Among 37 patients with assessable disease, there were 3 complete and 11 partial responses (response rate, 38%).. LV modulation of 5-FU can be incorporated safely into combination chemotherapy with epirubicin and provides a relatively active regimen for treatment of disseminated gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy.. Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy.. Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months.. This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Feasibility Studies; Female; Floxuridine; Fluorouracil; Humans; Infusions, Intravenous; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Pilot Projects; Stomach Neoplasms; Survival Analysis; Treatment Outcome

In September 1987 a phase II study was begun to verify if elderly symptomatic patients affected by advanced gastric cancer could benefit from a combination of 5-fluorouracil (5FU) and leucovorin (LV). We employed Machover's regimen: 5FU 370 mg/m2 i.v. infusion daily for 5 days; LV 200 mg/m2 i.v. bolus daily for 5 days; cycles were repeated every 3 weeks. 23 patients entered the study and 22 were evaluable for response and toxicity. We obtained only one partial response; 9 had stable disease and 12 progressed on therapy. The median duration of survival was 6 months. Symptoms were not affected by treatment. These data reflect the absence of significant improvement in the quality of life, which was further lessened by the presence of treatment side effects. Because of this we think that this regimen cannot be recommended for the treatment of elderly advanced gastric cancer patients.

Topics: Adenocarcinoma; Aged; Aging; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Stomach Neoplasms

The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer.. Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis.. Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04).. FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Cisplatin; Combined Modality Therapy; Doxorubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Prospective Studies; Stomach Neoplasms; Survival Analysis

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dipyridamole; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Drug Synergism; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasms; Stomach Neoplasms; Stomatitis

Twenty patients with metastatic gastric cancer were treated with methotrexate (MTX, M), 100 to 160 mg/m2 at 0 h, and, in sequence, 5-fluorouracil (FU, F), 600 to 1000 mg/m2 at 4 h; leucovorin (LV, L), 200 mg/m2 at 18 h, then 20 mg/m2 every 6 h x 12; 5-fluorouracil, 600 mg/m2 at 19 h; and high-dose cisplatin (DDP, P), 100 mg/m2 at 20 h. In addition, they were treated with a continuous 5-fluorouracil infusion, 1000 mg/m2/24 h from 18 h to 114. There were 8 complete and 6 partial responses among the 16 patients with measurable tumors. Five patients, each with one remaining clinical site of disease, received supplementary regional therapy: three received intraperitoneal therapy, two received hepatic arterial therapy. Intraperitoneal therapy and hepatic artery therapy each produced one complete response. Median survival was 16 months for all patients, and 25% survived 2 years. In comparison with matched patients, both response rates and survival improved twofold.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Folic Acid Antagonists; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Stomach Neoplasms

Thirty previously untreated patients with advanced measurable gastric cancer were given a combination chemotherapy consisting of 5-fluorouracil, 400 mg/m2, and leucovorin, 200 mg/m2 iv on days 1 to 3, mitomycin-C, 10 mg/m2 on day 1 (every other cycle) and adriamycin, 40 mg/m2 on day 2, repeated every 21 days. The overall response rate was 46% (14/30; 95% confidence limits: 28%-64%) including 4 patients with a complete remission. Eight patients progressed. Median duration of remission (CR+PR) was 10 months, with a median survival of 13, 8 and 4 months for CR+PR, NC and PD, respectively. Main toxicities were leukopenia (WHO grade III-IV in 36% of the patients) and alopecia. One patient died from myocardial infarction after an adriamycin cumulative dose of 480 mg/m2. No other treatment-related death occurred. L-FAM2 is an effective combination for advanced gastric carcinoma. Further studies based on the association of leucovorin and 5-fluorouracil in combination with other active drugs are warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Staging; Remission Induction; Stomach Neoplasms

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Infusions, Intravenous; Japan; Leucovorin; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Survival Rate

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Administration Schedule; Female; Fluorouracil; Humans; Japan; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Multicenter Studies as Topic; Nausea; Prospective Studies; Quality of Life; Random Allocation; Remission Induction; Stomach Neoplasms; Vomiting

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Drug Administration Schedule; Drug Evaluation; Fluorouracil; Humans; Leucovorin; Pancreatic Neoplasms; Stomach Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Mitomycin; Mitomycins; Stomach Neoplasms

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Kinetics; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms; Time Factors

Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen has shown strong efficacy as perioperative therapy for patients with locally advanced gastric (GC) and gastroesophageal (AEG) carcinoma. In the palliative situation, FLOT is recommended only for young fit patients. Data of efficacy and tolerability of FLOT in elderly patients are scarce and controversial. Thus, this study aimed to provide real-life experience of elderly patients with GC and AEG treated with FLOT as first-line palliative chemotherapy.. Patients with advanced or metastatic GC or AEG and treated with FLOT as first-line palliative therapy between 2010 and 2021 were analyzed. Patients were grouped into < 65 years old (n = 35) and ≥ 65 years old (n = 22) groups. Overall survival (OS), progression-free survival (PFS), feasibility and toxicity were analyzed.. The median OS was 10.4 months with no significant difference between both groups (HR 0.86; 95% CI 0.48, 1.57; p = 0.632). The ECOG performance status showed powerful influence on OS in the subgroup analysis with median OS of 12.3 months for ECOG = 0 compared to 5.0 months for ECOG ≥ 1 (p = 0.015) as well as in multivariate analysis (HR 2.62; 95% CI 1.36, 5.04; p = 0.004).. In the present study the ECOG performance status showed a stronger prognostic value than patient age in FLOT as first- line therapy in a real-life cohort with advanced and metastatic GC and AEG. The performance status should therefore be considered in the therapeutic decision making of elderly patients with GC and AEG.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution.. Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups.. Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023).. Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Retrospective Studies; Stomach Neoplasms

In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT.. Paired biopsy (PRE) and surgical (POST) samples of 25 patients treated with FLOT were prospectively analyzed. After collection of clinic-pathological data, NanoString analyses were performed. The primary objective of the study was to assess the changes induced by chemotherapy in POST compared to PRE samples.. The unsupervised hierarchical method analysis clearly distinguished PRE and POST samples, even though some cases showed high immune gene expression at baseline. When POST samples were compared with PRE, a differential expression in hyper-expressed gene sets related to cytotoxicity, T-cell functions, complement system, tumor necrosis factor superfamily, cell cycle, and regulation was recognized. Downstaging of the primary tumor (T-regression, measured by pathologic compared to clinical T stage) was the covariate most frequently associated with these changes. Using the immune cell profiling, cases with T-regression reported a significant increase of T, CD8+ T and B cells and a decrease in mast cells, while nonresponders demonstrated an increase of T, B, cytotoxic, and mast cells.. Our analysis shows that FLOT significantly influences immune TME of GC. While relevant modifications preferentially occur in tumors showing primary tumor regression, response to treatment seems to be associated with a specific immune profile.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Tumor Microenvironment

Gastric cancer (GC) is the fifth most frequent malignancy and the fourth leading cause of worldwide cancer-related death. Despite the usage of multimodal perioperative chemotherapy (pCT), GC progressively gains chemoresistance, thereby, the identification of suitable targets to overcome drug resistance is fundamental. Amongst the potential biomarkers, carbonic anhydrase IX (CAIX) - associated with a poor prognosis of several solid cancers - has gained the most attention. In a cohort of GC patients who received perioperative FLOT (i.e., Leucovorin, 5-Fluouracil, Docetaxel, and Oxaliplatin) or FOLFOX (i.e., Leucovorin, 5-Fluouracil, and Oxaliplatin), non-responder patients showed an increased expression of tumor CAIX compared to responder group. Moreover, GC cell lines induced to be resistant to 5-Fluouracil, Paclitaxel, Cisplatin, or the combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel, overexpressed CAIX compared to the control. Accordingly, CAIX-high-expressing GC cells showed increased therapy resistance compared to low-expressing cells. Notably, SLC0111 significantly improved the therapy response of both wild-type and resistant GC cells. Overall, these data suggest a correlation between CAIX and GC drug resistance highlighting the potential of SLC-0111 in re-sensitizing GC cells to pCT.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IX; Cell Line; Cell Line, Tumor; Docetaxel; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms; Taxoids

Platinum + fluoropyrimidine is a standard front-line therapy for unresectable gastroesophageal adenocarcinoma (GA). Subsequent therapy recommendations are ramucirumab + paclitaxel (RAM/PAC), taxane, irinotecan, or trifluridine-tipiracil. RAM/PAC is the preferred second-line choice; however, patients can have a contraindication due to cumulative neuropathy. Our study assessed varied sequencing of second-line and third-line therapies comparing RAM/PAC followed by fluoropyrimidine + irinotecan (FOLFIRI/CAPEIRI) versus the opposite sequence.. We retrospectively analyzed metastatic GA patients who received at least 3 lines of therapy. Two cohorts were studied. Group A: RAM/PAC second-line with FOLFIRI/CAPEIRI third-line or group B: FOLFIRI/CAPEIRI second-line followed by RAM/PAC. Primary outcome was overall survival (OS).. Ninety-four patients were available for analysis (51 pts group A: 43 pts group B). No difference was observed in median OS from the start of second-line therapy (group A = 10.5 months vs. group B = 11.1 months, p = 0.97) or median OS from metastatic disease diagnosis (group A = 19.8 months vs. group B = 19.4 months, p = 0.73).. Our study, examining a practical issue of how to sequence second- and third-line therapies, documents that one sequence versus the other does not compromise patient outcomes and overall, our patients had an outstanding OS of beyond 19 months when they receive third-line therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Young Adult

We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties.. We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety.. The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%).. Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Carcinoembryonic Antigen; Disease-Free Survival; Docetaxel; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Perioperative Period; Proportional Hazards Models; Stomach Neoplasms

Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)).. Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed.. Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality.. In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Cohort Studies; Docetaxel; Epirubicin; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Perioperative Care; Propensity Score; Stomach Neoplasms; Treatment Outcome

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Middle Aged; Oxaliplatin; Receptor, ErbB-2; Retrospective Studies; Stomach Neoplasms; Trastuzumab

We aimed to compare the efficacy and the safety of the FOLFOX and the FLOT regimens in metastatic gastric cancer (mGC) as first-line treatment. It was a retrospective multicenter observational study. The comparisons between groups were conducted in terms of progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and hematologic adverse events. Seventy-nine patients, diagnosed with mGC between March 2012 and December 2019, treated with FOLFOX (n = 43) or FLOT (n = 36) regimens as first-line treatment were included in the study. The mPFS was 10.9 months [95% confidence interval (CI), 5.8-16.1] in the FLOT arm and 7.1 months (95% CI, 5.1-9.1) in the FOLFOX arm (P < 0.001). The ORR was 63.9% in the FLOT arm and 30.2% in the FOLFOX arm (P = 0.003). The mOS was 13.3 months (95% CI, 11.3-15.4) in the FLOT arm and 10.9 months (95% CI, 8.2-13.5) in the FOLFOX arm (P = 0.103). The hematologic adverse events in all grades were 88.4% (n = 38) in the FOLFOX arm compared with 80.6% (n = 29) in the FLOT arm (P = 0.335). The FLOT regimen might be a preferred option in mGC with an improved PFS and ORR compared with the FOLFOX regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophagogastric Junction; Female; Fluorouracil; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Stomach Neoplasms; Survival Analysis

The aim of this study was to show that the Controlling Nutritional Status (CONUT) score has predictive value in gastric cancer (GC) patients treated with perioperative fluorouracil, leucovorin, oxaliplatin, or docetaxel (FLOT).. A total of 161 GC patients treated with perioperative FLOT in our center were included in the study. The ideal cutoff values for the CONUT score were obtained using the receiver operating characteristic (ROC) curve analysis, and the patients were divided into low (≤3) and high (> 3) CONUT groups. The associations of CONUT with clinicopathological factors and survival were evaluated retrospectively.. The median follow-up time was 11.2 months (2.3-32.3 months). The median overall survival (OS) for the entire population was 14.7 months (95% CI 13.5-15.9 months). Median OS was not reached in the low-CONUT group, but it was 14.2 months (95% CI 12.6-15.9) in the high-CONUT group and the difference was statistically significant (p = 0.002). The univariate Cox proportional hazards model revealed that OS was significantly associated with Eastern Cooperative Oncology Group (ECOG) status (p < 0.001), T4b stage (p 0.03), modified Glasgow Prognostic Scores (mGPS) (p 0.005), prognostic index (PI) (p 0.011), prognostic nutritional index (PNI) (p < 0.001), CONUT score (p 0.003), and mucinous histology (p 0.004). In multivariate analysis, ECOG performance status (p 0.029), PNI (p 0.001), CONUT score (p 0.040), and mucinous histology (p 0.001) were still identified as independent prognostic factors for OS.. Our study demonstrated the prognostic significance of the CONUT score in GC patients treated with perioperative FLOT.

Topics: Docetaxel; Fluorouracil; Humans; Leucovorin; Nutritional Status; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms

Perioperative chemotherapy (POC) in advanced gastric cancer (GC) patients significantly increases the curative resection rate and overall survival (OS). Textbook outcome (TO) represents a composite of surgical quality metrics strongly associated with improved OS. However, the current definition of TO after resection for GC does not include POC. Herein we propose to supplement the current description of TO with an additional feature, POC compliance. The present study aimed to evaluate prognostic impact of thus defined textbook oncological outcome (TOO) among patients undergoing gastrectomy for advanced GC.. We collected data from a prospectively maintained database of all patients operated for GC between 2010 and 2020 in our institution. Patients with histologically confirmed and resectable advanced GC but without distant metastases, in whom multimodal treatment was planned by institutional MDT were included.. A total of 194 patients were analyzed. In the multivariate analysis, patients with TOO had a 50 % lower risk of death than patients without TOO (medians: NR vs 42 months; HR = 0.50, p = 0.0109). Patients treated with POC had a 43 % lower risk of death than patients treated with only preoperative chemotherapy (medians: 78 vs 33 months; HR = 0.57, p = 0.0450). Patients with a pathological response (PR) in the primary tumor had a 59 % lower risk of death than patients without PR (medians: NR vs 36 months; HR = 0.41, p = 0.0229). POC combined with TO surgery significantly decreased the risk of death in advanced GC patients (medians: NR vs 42 months; HR = 0.35, p = 0.0258).. Since TOO is associated with improved survival, it may serve as a multimodal treatment quality parameter in patients with advanced GC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Docetaxel; Epirubicin; Female; Fluorouracil; Gastrectomy; Guideline Adherence; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Outcome and Process Assessment, Health Care; Oxaliplatin; Perioperative Care; Postoperative Complications; Practice Guidelines as Topic; Stomach Neoplasms; Survival Rate

Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity.. Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms.. Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity.. Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Case-Control Studies; Confidence Intervals; Dihydrouracil Dehydrogenase (NADP); DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Gene Frequency; Genes, p53; Genotype; Glutathione S-Transferase pi; Glycine Hydroxymethyltransferase; Humans; Leucovorin; Logistic Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Multienzyme Complexes; Nomograms; Odds Ratio; Organoplatinum Compounds; Orotate Phosphoribosyltransferase; Orotidine-5'-Phosphate Decarboxylase; Platinum Compounds; Polymorphism, Single Nucleotide; Pyrimidines; Quality of Life; Retrospective Studies; Stomach Neoplasms; Xeroderma Pigmentosum Group D Protein

We report a case of advanced gastric cancer that was successfully treated with mFOLFOX6 therapy. A 78-year-old man presented to our hospital with a chief complaint of weight loss. Esophagogastroduodenoscopy(EGD)and computed tomography( CT)revealed the presence of type 3 advanced gastric cancer with distant lymph node metastasis and peritoneal dissemination. Biopsy specimen examination revealed moderately differentiated adenocarcinoma with a HER2 score of 1. Chemotherapy comprising 5-fluorouracil, Leucovorin, and oxaliplatin(mFOLFOX6)was administered because of renal failure. Subsequently, the gastric lesion, distant lymph node metastasis, and peritoneal dissemination were seen to be reduced on EGD and CT. After 7 courses, the regimen was changed to 5-fluorouracil and Leucovorin(5-FU/l -LV)chemotherapy because of thrombocytopenia. For more than 10 months, he has continued to receive chemotherapy without the recurrence of metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Recurrence, Local; Organoplatinum Compounds; Stomach Neoplasms

Traditional Chinese medicine injections (TCMJs) combined with FOLFOX4 regimen could achieve favorable effects in the treatment of gastric cancer. However, the efficacy and safety of different TCMJs combined with FOLFOX4 in the treatment of gastric cancer have not been fully clarified. Due to the fact that there are as many as 10 kinds of TCMJs, how to choose an appropriate TCMJ has become an urgent clinical problem. The objective of this network meta-analysis is to explore the optimal options among different TCMJs for gastric cancer.. PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data were searched to identify randomized controlled trials which focused on TCMJs combined with FOLFOX4 against gastric cancer from its inception to September 2021. Subsequently, 2 researchers will be independently responsible for literature screening, data extraction, and assessment of their quality. Standard pair-wise and Bayesian network meta-analysis will be performed to compare the efficacy and safety of different TCMJs combined with FOLFOX4 regimen via Stata 14.0 and WinBUGS1.4 software.. The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.. The conclusion of this systematic review will provide evidence for selecting an optimal TCMJ combined with FOLFOX4 for patients with gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; China; Combined Modality Therapy; Female; Fluorouracil; Humans; Injections; Leucovorin; Male; Medicine, Chinese Traditional; Meta-Analysis as Topic; Network Meta-Analysis; Organoplatinum Compounds; Randomized Controlled Trials as Topic; Safety; Stomach Neoplasms; Systematic Reviews as Topic; Treatment Outcome

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3 h prior to the start of a 4 h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7 L and 30.0 μg·h/mL, respectively. A dose reduction of L-OHP by 30%-50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Fluorouracil; Humans; Kidney Failure, Chronic; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Renal Dialysis; Stomach Neoplasms

Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery.. The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival.. The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273).. Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes.. Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT.. A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1;. Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.

Topics: Antineoplastic Combined Chemotherapy Protocols; Body Composition; Body Mass Index; Combined Modality Therapy; Docetaxel; Female; Fluorouracil; Humans; Italy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Retrospective Studies; Sarcopenia; Stomach Neoplasms; Tomography, X-Ray Computed

The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult.. We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable.. Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed.. R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively.. This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Female; Fluorouracil; Gastrectomy; Gastric Bypass; Gastric Outlet Obstruction; Humans; Infusions, Intravenous; Laparoscopy; Leucovorin; Lymph Nodes; Male; Middle Aged; Neoplasm Grading; Omentum; Oxaliplatin; Retrospective Studies; Stomach Neoplasms

We aimed to determine the predictive significance of Ki-67 and platelet lymphocyte ratio (PLR) in patients with gastric cancer (GC), who received fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) as neoadjuvant chemotherapy (NAC).. Descriptive study.. Department of Medical Oncology, Faculty of Medicine,  Ondokuz Mayıs University, Samsun, Turkey from March 2016 to January 2020.. Seventy-five patients with GC, who received FLOT treatment as NAC were included in the study. Ki-67 and PLR, which were examined pre-NAC and aft-NAC, were recorded. Associations between clinical-histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analysed using Kaplan-Meier curves. Cox-regression analysis was used to assess their prognostic values.. There was a statistically significant difference between pre-NAC and aft-NAC Ki-67, and aft-NAC PLR values between groups with complete response, partial response, and stable disease aft-NAC (p: 0.023, p: <0.001; and p: 0.001, respectively). When the patients were grouped according to the pre-NAC and aft-NAC Ki-67 changes, a significant difference was found in terms of OS (p< 0.001). High pre-NAC and high aft-NAC Ki-67 were associated with shorter DFS and OS (p: 0.042, p: 0.049; p: 0.027, and p: 0.001, respectively). The high pre-NAC PLR was associated with shorter OS, while the high aft-NAC PLR was associated with shorter DFS (p: 0.018, and  p: 0.001, respectively). In multivariate analysis, aft-NAC Ki-67 was found to be an independent prognostic factor for OS.. Ki-67 and PLR have predictive significance in GC patients treated with neoadjuvant FLOT. Ki-67 is an independent prognostic marker for OS in gastric cancer. Key Words: FLOT, Gastric cancer, Ki-67, Platelet lymphocyte ratio.

Topics: Docetaxel; Fluorouracil; Humans; Ki-67 Antigen; Leucovorin; Lymphocytes; Neoadjuvant Therapy; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms; Turkey

The predictive value of mismatch repair protein deficiency (MMRD) for chemoradiotherapeutic outcome has rarely been reported in gastric cancer. This study investigated the clinical significance of MMRD as a prognostic factor for tumor recurrence, and as a predictor of response to adjuvant chemoradiotherapy in advanced gastric cancer patients.. Between 1995 and 2008, tissue specimens of 881 patients who underwent radical gastrectomy for stage II and III gastric cancer were analyzed. MMRD was assessed using immunohistochemical stains for MLH1, PMS2, MSH2, and MSH6. Patients were divided into two groups according to adjuvant treatment: a 5-fluorouracil/leucovorin (FL) adjuvant chemoradiotherapy group and a surgery alone group. Disease-free survival (DFS) was compared between the two groups correlated to MMRD. Risk factors for tumor recurrence were analyzed using multivariate analysis.. Of the 881 gastric cancer patients, 88 (10.0%) exhibited MMRD and 398 (45.2%) patients received adjuvant FL chemoradiotherapy. The multivariate analysis revealed that MMRD was a good independent prognostic factor (hazard ratio, 0.572; 95% confidence interval, 0.370-0.883; P = 0.012). For stage III gastric cancer displaying mismatch repair protein proficiency (MMRP), adjuvant FL chemoradiotherapy after surgery resulted in better DFS than surgery alone (P = 0.001). Among the stage II gastric cancer patients, adjuvant FL chemoradiotherapy did not show survival benefit, regardless of MMRD.. MMRD is a good independent prognostic factor in advanced gastric cancer. Adjuvant FL chemoradiotherapy was beneficial in patients with stage III gastric cancer with MMRP but not in those with MMRD.

Topics: Adult; Aged; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; DNA Mismatch Repair; Female; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Risk Factors; Stomach Neoplasms

Hemoglobin (HB) and red cell distribution width (RDW) are known to be prognostic in many cancer types. The HB-RDW ratio (HRR) is a new biomarker that has been shown to be predictive in some cancer types. However, the prognostic significance of HRR in patients with gastric cancer (GC) is unknown.. In this study, we aimed to demonstrate the prognostic importance of HRR in GC patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT).. Eighty-five GC patients who were treated with neoadjuvant FLOT in our center were included in the study, retrospectively. Associations between clinical and histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and HRR were grouped based on a cutoff points 3.05, 802, and 0.89, respectively. Univariate and multivariate analyses were used to assess their prognostic values for DFS and OS.. Low NLR, low SII, and high HRR were found to be associated with longer DFS/OS. In univariate analysis, Eastern Cooperative Oncology Group performance status, grade, stage, response to neoadjuvant treatment, NLR, SII, and HRR were found to be significantly associated with DFS and OS. But in multivariate analysis, only HRR was demonstrated as an independent prognostic factor for DFS/OS (p 0.001, p 0.037, respectively).. HRR is a new biomarker that can predict DFS and OS in GC patients treated with neoadjuvant FLOT.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Erythrocyte Indices; Female; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Retrospective Studies; Stomach Neoplasms; Survival Analysis

Topics: Adenocarcinoma; Capecitabine; Cisplatin; Docetaxel; Epirubicin; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

Topics: Adenocarcinoma; Capecitabine; Cisplatin; Docetaxel; Epirubicin; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

FOLFOX therapy has been used for gastric cancer in Japan since 2017. We retrospectively analyzed the efficacy of FOLFOX therapy compared to that of FP. Forty-seven cases were evaluated between January 2010 and December 2018. Eighteen patients received mFOLFOX6 therapy, and 29 patients received FP therapy. The median time to treatment failure was 206 days in the mFOLFOX6 group and 58 days in the FP group. The response rate was 50% in the mFOLFOX6 group and 17% in the FP group. Neutropenia(56%), thrombocytopenia(50%), and peripheral neuropathy(56%)were the common adverse events in the mFOLFOX6 group, and leukopenia(69%)and neutropenia(69%)were the common adverse effects in the FP group. Based on our results, we conclude that, unlike FP, FOLFOX is an effective therapy for of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Fluorouracil; Humans; Japan; Leucovorin; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

The prognosis of patients with advanced gastric cancer remains unsatisfactory, highlighting the need for improved therapeutic strategies. We analyzed 23 resectable advanced gastric cancer patients who received FLOT followed by laparoscopic gastrectomy with D2 lymphadenectomy to evaluate the efficacy and safety.. Patients aged 18-75 years with gastric adenocarcinoma (stage cT3-4 and/or N + M0) underwent neoadjuvant FLOT therapy (four preoperative and four postoperative 2-week cycles) at Shanghai East Hospital. Laparoscopic gastrectomy was scheduled 3-4 weeks after completion of the last cycle of preoperative chemotherapy. The type of surgical procedure was determined by the location and extent of the primary tumor.. 23 patients were reviewed in the study. 20 patients (81.2%) received four courses of FOLT therapy, while 3 patients (18.8%) received three courses of treatment. There were 3 (13.0%) complete responses, 13 (56.5%) partial responses, 4 (26.1%) of stable disease, and 1 (4.3%) of progressive disease. The clinical efficacy response rate was 69.6%. The R0 resection rate was 91.3%. Only one patient exhibited grade III postoperative complications. The pathologic complete remission was 13%. The common grade 3/4 adverse events from chemotherapy were leucopenia (17.4%), neutropenia (30.4%), anemia (13%), anorexia (13%), and nausea (17.4%). Postoperative complications occurred in 5 patients (26.1%). There was no treatment-related mortality or reoperation. The most reason for not completing chemotherapy was the patient's request.. These findings suggest that FLOT neoadjuvant chemotherapy, followed by laparoscopic D2 gastrectomy, is effective and safe in advanced, resectable advanced gastric cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Female; Fluorouracil; Gastrectomy; Humans; Laparoscopy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Stomach Neoplasms; Treatment Outcome; Young Adult

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Female; Fluorouracil; Humans; Leucovorin; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome; Tumor Microenvironment

Topics: Cisplatin; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms; Tegafur

Chemotherapy is used as an indispensable therapy for advanced gastric cancer. Different chemotherapy regimens have been used for this purpose. Toxicity due to the Chemotherapy drugs is one limiting factor. In this study we aim to compare the efficacy and toxicity of two regimens FOLFOX (leucoverin, 5-fluorouracil and oxaliplatin) and modified DCF (mDCF) (docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced gastric adenocarcinoma.. In this analytical cross-sectional study, 47 patients treated with FOLFOX regimen and 57 patients treated with mDCF regimen were recruited, Patients in both groups were compared for demographic findings, response rate, mortality rate, overall survival (OS) and progression free survival (PFS).. In FOLFOX and mDCF group, complete response (CR) occurred in 4.3% and 5.3%, partial response (PR) in 42.6% and 29.8%, stable disease in 34% and 52.6% and disease progression in 19.1% and 12.3%, respectively (p=0.25). Overall response rate was 48.9% and 56.1%, respectively. There was no significant difference between two regimens in OS and PFS (p=0.22). mDCF compared to FOLFOX had significantly higher hematologic, gastrointestinal complications, as well as creatinine rise, stomatitis and hair loss, but peripheral neuropathy was significantly lower.. The results of current study showed that in patients with advanced gastric adenocarcinoma, FOLFOX regimen compared to mDCF regimen have similar ORR, OS and PFS. Toxicity rate are also lower in FOLFOX group, thus it seems a better regimen for chemotherapy.
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Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cross-Sectional Studies; Docetaxel; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

A 42-year-old woman was referred to our hospital for the treatment of pyloric stenosis. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) revealed the presence of type 4 advanced gastric cancer with bladder metastasis and peritoneal dissemination. Biopsy specimen examination revealed poorly differentiated adenocarcinoma with signet ring cell carcinoma. Thus, two cycles of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin were administered. Subsequently, the gastric lesion and bladder metastasis reduced as detected using EGD and CT. Consequently, she achieved adequate oral intake. After changing the regimen to tegafur/gimeracil/oteracil and oxaliplatin, she was discharged. Currently, she continues to receive chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Organoplatinum Compounds; Stomach Neoplasms; Urinary Bladder; Urinary Bladder Neoplasms

We describe the case of a 74-year-old woman with previous history of gastric signet cell carcinoma who develops bladder metastasis as first sign of recurrence 6 years later. Bladder metastasis due to signet cell carcinoma is extremely rare with only 19 cases reported. Treatment includes radical cystectomy or chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Cystectomy; Female; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Leucovorin; Neoplasm Staging; Neoplasms, Second Primary; Organoplatinum Compounds; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Urinary Bladder Neoplasms

To investigate the efficacy of paclitaxel combined with a leucovorin and 5-fluorouracil regimen (PLF regimen; q2w) as neoadjuvant chemotherapy (NCT) for advanced gastric cancer.. A total of 183 patients with advanced gastric cancer who underwent 3 cycles of PLF regimen chemotherapy before surgery and received surgery 2 weeks after chemotherapy were enrolled as a treatment group. A total of 184 patients with advanced gastric cancer and no NCT during the same period were enrolled as the controls and treated with surgery. Both groups underwent a D2 radical gastrectomy and the standard postoperative adjuvant chemotherapy.. In the NCT group, there were 19 cases of complete remission, 86 cases of partial remission, 72 cases of stable disease, and 6 cases of progressive disease, with an overall response rate of 57.4%. The R0 resection rate was higher than in the control group (85.2% vs 61.4%,. The PLF regimen showed good tolerability and a high response rate, especially for esophagogastric cancer. This regimen reduced the tumor size, lowered the tumor stage, and improved the R0 resection rate and survival rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

The aim of this retrospective analysis was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, 5-fluorouracil, and leucovorin (TFL) as first-line treatment in patients with advanced gastric cancer (AGC). One hundred and thirteen patients were enrolled in the study who were confirmed to have AGC by histopathology. These patients were treated with TFL: paclitaxel at a dose of 135 mg/m as a 3-h intravenous infusion on day 1, LV 400 mg/m as an intravenous infusion over 2 h on day 1, followed by 5-fluorouracil 2400 mg/m as an infusion over a 46-h period on 3 consecutive days. Cycles were repeated every 2 weeks. A total of 113 patients were assessed for their response to therapy. A total of three patients achieved complete responses and 46 patients achieved partial responses, yielding an overall objective response rate of 43.4% [95% confidence interval (CI): 34.3-52.5%]. Fifty-four cases of stable disease and 10 cases of progressive disease were observed in the remaining patients. The median time to progression and overall survival were 5.2 months (95% CI: 4.7-5.8 months) and 14.1 months (95% CI: 12.5-15.8 months), respectively. Toxicities were tolerable and moderate. The most common grade 3-4 toxicities included leukopenia (16.8%), neutropenia (17.7%), anemia (8.0%), thrombocytopenia (5.3%), and fatigue (6.2%). Combination chemotherapy with TFL offers an active and safe therapeutic approach for patients with AGC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Young Adult

Gastric cancer patients are normally treated with oral fluoropyrimidine and cisplatin or oxaliplatin; however, treating patients who also have a gastrointestinal obstruction is often difficult because of their poor oral intake. Instead, a modified (m)FOLFOX-6 regimen is administered, even to patients with gastrointestinal obstructions. The aim of this study was to assess the efficacy of mFOLFOX-6 for gastric cancer patients with a gastrointestinal obstruction.. Patients with a poor oral intake because of a gastrointestinal obstruction who received mFOLFOX-6 as systemic chemotherapy were retrospectively analyzed. Poor oral intake was defined as receiving a daily intravenous drip infusion due to a gastrointestinal obstruction.. Eighteen patients received mFOLFOX-6; the median progression-free survival was 6.8 months (95% confidence interval [CI], 1.9-9.7), the median overall survival was 8.0 months (95% CI, 2.8-20.8) and the median time to treatment failure was 2.2 months (95% CI, 1.2-5.7). An improved oral intake was observed in 13 of the 18 treated patients, with 12 of these continuing treatment as outpatients.. A mFOLFOX-6 treatment regimen seems promising for gastric cancer patients who have a gastrointestinal obstruction.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Intestinal Obstruction; Leucovorin; Male; Middle Aged; Oxaliplatin; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients and chemotherapy resistance is the major obstacle to effective cancer therapy. Increasing evidence suggests that mesenchymal stem cells (MSCs) make important contributions to development of drug resistance. However, the underlying mechanism remains elusive. In this study, we discovered that abundant MSCs in tumor tissues predicted a poor prognosis in GC patients. MSCs promoted stemness and chemoresistance in GC cells through fatty acid oxidation (FAO) in vitro and in vivo. Mechanically, transforming growth factor β1 (TGF-β1) secretion by MSCs activated SMAD2/3 through TGF-β receptors and induced long non-coding RNA (lncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p. Moreover, pharmacologic inhibition of FAO with etomoxir (ETX) attenuated MSC-induced FOLFOX regiment resistance in vivo. These results suggest that FAO plays an important role in MSC-mediated stemness and chemotherapy resistance in GC and FAO inhibitors in combination with chemotherapeutic drugs present as a promising strategy to overcome chemoresistance.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cells, Cultured; Drug Resistance, Neoplasm; Fatty Acids; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Lipid Metabolism; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Organoplatinum Compounds; Oxidation-Reduction; RNA, Long Noncoding; Stomach Neoplasms; Trans-Activators; Transcription Factors

Tumor size has been regarded as the "T" stage of many solid tumors because of its effect on prognosis. However, the prognostic impact of tumor size in gastric cancer (GC) is still controversial.. A total of 436 patients with curatively resected GC and those without lymph node metastasis in our center were retrospectively enrolled. The appropriate cutoff points for tumor size were determined. Potential prognostic factors were analyzed. In addition, a pathological tumor-size (pTS) classification system was proposed to evaluate the superiority of its prognostic prediction of node-negative GC patients compared with that of the pT staging system.. The ideal cutoff points for tumor size were 4 and 8 cm. In the multivariate analysis, tumor size was identified as an independent prognostic factor for node-negative GC patients after surgery, as was pT stage. The pTS classification was found to be more appropriate for predicting the overall survival of node-negative GC patients after curative surgery than pT stage, and the -2 log-likelihood of the pTS classification (1680.782) was smaller than the value of pT (1695.239).. As an independent prognostic factor, tumor size should be incorporated into the pT staging system to enhance the accuracy of the prognostic prediction of node-negative GC patients.

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Prognosis; Retrospective Studies; Stomach; Stomach Neoplasms; Treatment Outcome; Tumor Burden

Topics: Adenocarcinoma; Capecitabine; Cisplatin; Docetaxel; Epirubicin; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

A 60-year-old woman presented to our department with severe tongue pain. On initial examination, the mucosal surface of the tongue was intact but a hard submucosal mass on the dorsum of the tongue was detected on palpation. Magnetic resonance imaging demonstrated an ill-defined tumor in the intrinsic tongue muscles. Sequential whole-body positron emission tomography/computed tomography revealed a tumor of the pancreas apart from the tongue lesion, and upper gastrointestinal endoscopy revealed gastric mucosa ulceration. On biopsy, the tongue lesion was confirmed to be metastatic gastric adenocarcinoma, and the gastric ulcer was simultaneously diagnosed as poorly differentiated gastric adenocarcinoma. The definitive diagnosis was thus gastric adenocarcinoma and synchronous pancreatic cancer, with gastric carcinoma metastases to the tongue. We administered FOLFIRINOX treatment for pancreatic cancer and FLTAX treatment for gastric cancer. Because of difficulty with oral intake due to the growth of the tongue lesion, we administered palliative radiation therapy at a dose of 30 Gy in 10 fractions following which the patient was able to resume oral intake and was satisfied with this outcome. She died 8 months after her first visit to our department.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastric Mucosa; Glossalgia; Humans; Irinotecan; Leucovorin; Middle Aged; Oxaliplatin; Prognosis; Stomach Neoplasms

There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes.. This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy.. Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable.. Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Malnutrition; Methotrexate; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Peritoneal Neoplasms; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment; Young Adult

Topics: Adenocarcinoma; Antibodies, Monoclonal; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Stomach Neoplasms

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first- and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m² irinotecan and 400 mg/m² leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m² 5-fluorouracil IV bolus then 2600 mg/m² continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: >2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Female; Fluorine; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Patient Safety; Platinum; Pyrimidines; Stomach Neoplasms; Taxoids; Treatment Outcome

A phase 3 trial of S-1, leucovorin (LV), and oxaliplatin for treating gastric cancer is now underway. However, the antitumor efficacy of the combination has not yet been examined in an in vivo preclinical study. This study examined the antitumor efficacy of combination therapy consisting of S-1, LV, and oxaliplatin against 4 human gastric cancer xenografts: NUGC-4, St-40, SC-2, and SC-4.. The antitumor efficacy was evaluated using human gastric cancer xenograft-bearing nude mice. S-1 and LV were administered orally once daily on days 1-7 at doses of 6.9 and 10 mg/kg, respectively. Oxaliplatin was administered intravenously at a dose of 8.3 mg/kg on day 1. The tumor volume was measured on day 15, and the relative tumor volume (RTV) was calculated.. In all 4 xenograft models, S-1 alone and oxaliplatin alone, but not LV alone, had significant antitumor activities (p < 0.001). Combination therapy consisting of S-1 and LV resulted in a significantly smaller RTV than S-1 alone (p < 0.001). Combination therapy consisting of S-1 and oxaliplatin also resulted in a significantly smaller RTV than either S-1 alone (p < 0.001) or oxaliplatin alone (p < 0.001). Furthermore, combination therapy consisting of S-1, LV, and oxaliplatin resulted in the highest antitumor activity in these models (p < 0.001 vs. S-1 + LV; p < 0.001 or p = 0.003 vs. S-1 + oxaliplatin).. Combination therapy consisting of S-1, LV, and oxaliplatin administered according to a 1-week-on/1-week-off schedule may be useful for the treatment of patients with gastric cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Combinations; Drug Therapy, Combination; Humans; Leucovorin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Transplantation, Heterologous

Limited studies exist comparing clinical outcomes by adjuvant treatment for pT1N1 gastric cancer. This study compared the disease-free survival (DFS) of patients with pT1N1 gastric cancer according to the type of adjuvant treatment-surgery alone, chemotherapy (CTx), and chemoradiotherapy (CCRTx)-and evaluated risk factors for tumor recurrence.. Between 1995 and 2015, 738 patients underwent radical gastrectomy for pT1N1 gastric cancer and were divided into three groups: surgery alone (n = 355), CTx (n = 214), and CCRTx (n = 169). Chronological changes in adjuvant treatment type and chemotherapeutic regimens were evaluated and DFS was compared. Risk factors for tumor recurrence were analyzed.. The proportion of patients who underwent surgery alone was more than 50% until 2001, and the proportion of those who had either CTx or CCRTx was more than 50% from 2002 to 2011, after which the proportion who underwent surgery alone increased again. The main chemotherapeutic agent was 5-fluorouracil with leucovorin. The 5-year DFS was 96.5% in the surgery-alone group, 96.0% in the CTx group, and 95.8% in the CCRTx group (no significant difference). The various chemotherapeutic regimens did not show differences in DFS. In univariate and multivariate analyses, adjuvant CTx and CCRTx showed no beneficial effect with regard to tumor recurrence.. Because adjuvant CTx and CCRTx did not show any benefit with regard to tumor recurrence, these treatment strategies might be unnecessary for pT1N1 gastric cancer after gastrectomy. Further studies are necessary to reveal pT1N1 gastric cancer patient subgroups who might benefit from adjuvant treatments.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Oxaloacetates; Oxonic Acid; Pyridines; Radiotherapy Dosage; Stomach Neoplasms; Tegafur

There is limited data on third-line chemotherapy in patients with metastatic gastric cancer (MGC). This study was conducted to assess third-line treatment patterns, outcomes, and clinical parameters related to survival outcomes in patients with MGC.. Using the Korean Health Insurance Review and Assessment Service (HIRA) database, a nationwide population-based outcomes study was conducted. From the HIRA database, patients newly diagnosed in 2010 with MGC were identified (N = 1,871), and of these, 229 patients who had received third-line chemotherapy were finally selected for this study.. Prior to third-line chemotherapy, more than 90% of patients received fluoropyrimidine and platinum, and 43.7% and 40.6% received taxane and irinotecan, respectively. Various third-line chemotherapy regimens containing taxane (docetaxel or paclitaxel), irinotecan, or oxaliplatin were prescribed. The median overall survival (OS) of all patients receiving third-line chemotherapy was 4.4 months. The median time from the start date of first-line chemotherapy to the start date of third-line chemotherapy (TF1T3) was 9.5 months, and a longer TF1T3 was the only factor that was significantly associated with an increased OS. The median OS of patients who had received fluoropyrimidine, platinum, and taxane followed by third-line irinotecan-based therapy was similar to that of patients who had received fluoropyrimidine, platinum, and irinotecan followed by third-line taxane-based therapy (p = 0.894).. In patients with MGC receiving third-line chemotherapy, TF1T3 was the only significant factor associated with OS. The sequence of using taxane and irinotecan as subsequent therapy after first-line failure was not shown to impact survival outcome.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Databases, Factual; Disease-Free Survival; Docetaxel; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Stomach Neoplasms; Treatment Outcome

Although surgery is considered to be curative treatment, recurrence rates are high in gastric cancer. Adjuvant 5-fluorouracil (5-FU) based chemoradiotherapy has been shown to improve the prognosis. We compared tolerability and efficacy of the two different chemotherapy regimens; 5-FU/leucovorin (LV) versus cisplatin with capecitabine (XP) combined with radiotherapy (RT) in the adjuvant therapy of the lymph node positive locally advanced gastric cancer.. Totally, 104 patients who underwent curative surgery with lymph node resection were evaluated, respectively. Patients were stratified two group based on the adjuvant chemoradiotherapy regimen. Group 1 (n = 46) received XP followed capecitabine with RT (XRT) then XP. Group 2 (n = 58) received 5-FU/LV combined with RT postoperatively. Two groups were compared based on clinicopathological parameters. Factors related with disease-free survival (DFS) and overall survival (OS) were analyzed.. Totally, 32 patients had recurrent disease, and there was no difference between two groups. While peritoneal metastasis was more common in XP arm, distant metastasis was commonly seen in 5-FU/LV arm. There was no significant difference between two groups in regard of Grade 3/4 toxicitis; hematologic toxicities were more in 5-FU/LV group than XP arm. In addition, dose modification because of toxicities were more frequent in 5-FU/LV arm (P = 0.003). For all groups, lymph node dissection type was related with DFS, surgical margin and recurrence were important for OS.. XP-XRT regimen is well tolerated with lower toxicity compared the standard 5-FU/LV-RT. Although there is no difference with respect to outcome, patients with XP arm without the necessity of intravenous catheter admitted hospital less frequent than bolus5-FU/LV arm.

Topics: Adult; Aged; Capecitabine; Chemoradiotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymph Nodes; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Stomach Neoplasms

Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial.. We developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data.. The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone.. Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Cohort Studies; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Neoplasm Recurrence, Local; Neoplasm Staging; Stomach Neoplasms; Survival Rate

According to some guidelines for the management of gastric cancer, adjuvant chemotherapy is recommended for patients with pT3-4 or node-positive disease. The aim of this study was to define low- and high-risk groups in terms of survival, and to predict the benefit of adjuvant fluoropyrimidine plus oxaliplatin (F-OX) chemotherapy.. Patients with pT3-4 or node-positive gastric cancer after gastrectomy with D2 lymphadenectomy between 2000 and 2013 were included. The performance of a previously published nomogram was assessed by discrimination and calibration. Patients were stratified into risk groups on the basis of the nomogram-predicted overall survival probability. The efficacy of F-OX within each risk subgroup was assessed using the log rank test and Cox regression analysis weighted by inverse propensity score.. Some 1464 patients were included. The nomogram showed better discrimination than the seventh AJCC staging classification (concordance index 0·72 versus 0·68 respectively; P = 0·008) and accurate calibration. F-OX was not associated with improved survival in patients in the low-risk group, whereas it reduced the risk of death by over 20 per cent in the intermediate- and high-risk groups (P = 0·036 and P < 0·001 respectively) (P for interaction = 0·014).. A nomogram can aid in individualized decision-making regarding the administration of F-OX after gastrectomy for cancer.

Topics: Aftercare; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; China; Clinical Decision-Making; Deoxycytidine; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nomograms; Organoplatinum Compounds; Oxaloacetates; Patient Selection; Postoperative Care; Pyrimidines; Stomach Neoplasms

A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Disseminated Intravascular Coagulation; Female; Fluorouracil; Gastrectomy; Humans; Levoleucovorin; Stomach Neoplasms; Treatment Outcome

Severe peritoneal metastasis (PM) from advanced gastric cancer (AGC) causes massive ascites and inadequate oral intake. Because patients with severe PM are often not included in clinical trials, little is known regarding the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil (FOLFOX) for them.. We retrospectively studied AGC patients with massive ascites and/or inadequate oral intake due to severe PM treated with FOLFOX as the first-line treatment.. Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median progression-free and overall survivals were 7.5 and 13.2 months, respectively. Ascites decreased in seven of nine patients with ascites, and oral intake improved in four of seven patients with an inadequate oral intake. Common grade 3-4 adverse events included neutropenia and anemia.. This study suggests that FOLFOX is effective and manageable for AGC patients with severe PM.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

Recurrence of gastric cancer after 10 years of surgical resection is highly rare. There are limited data on the surveillance of patients with gastric cancer after 10 years from gastrectomy. A 50-year-old man presented to the gastroenterology clinic at our hospital for the management of abnormal findings on a routine colonoscopic exam. He had undergone gastrectomy for advanced gastric cancer 12 years ago. At presentation, colonoscopic examination revealed asymmetrically edematous and hyperemic mucosal change with luminal narrowing on transverse colon. Abdominal computed tomography showed no evidence of distant metastasis, except for focal bowel wall thickening on transverse colon. He underwent a laparoscopic right-hemicolectomy, and the resected specimen revealed a recurrent and metastatic lesion. We report a case of recurrence of gastric cancer after 10 years from surgical resection with relevant literature review.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonoscopy; Fluorouracil; Gastrectomy; Humans; Intestinal Mucosa; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Stomach Neoplasms; Tomography, X-Ray Computed

Disseminated intravascular coagulation (DIC) is a rare complication of advanced gastric cancer (AGC). Despite reports of the efficacy of chemotherapy for AGC with DIC, little is known of platinum-based doublet therapy.. We conducted a single-institute, retrospective chart review of 500 consecutive chemotherapy-naïve patients with advanced gastric adenocarcinoma (recurrent or metastatic) from November 2010 to November 2015.. Six patients were diagnosed with AGC with DIC (1.2%); five (1.0%; 3 men, 2 women) received platinum-based doublet chemotherapy. All patients exhibited improved DIC and thrombocytopenia and survived for >100 days (range=114-313) with no therapy-related mortality. Grade ≥3 adverse effects included neutropenia, anemia, hyponatremia, catheter-related infection and diarrhea (maximum: 2 patients each).. Fluoropyrimidine plus platinum combination therapy was effective against DIC and yielded acceptable survival outcomes. Combination chemotherapy should be considered as a primary therapy for AGC with DIC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients.. Using the patient cohort (. Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345;. The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Glucuronosyltransferase; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Metastasis; Stomach Neoplasms; Treatment Outcome; Vomiting

The incidence of the para-aortic lymph node metastasis (PALM) in patients with advanced gastric cancer is 6 to 33 %. The prognosis is poor and the 5-year survival rate is only 12 to 23 % after gastrectomy with super-extended lymph node dissection. We applied an individualized comprehensive treatment for affected patients including neoadjuvant chemotherapy via intra-arterial and intravenous administration, surgery and radiotherapy, to investigate the safety and prognostic value.. Between January 2005 and December 2010, 47 advanced gastric cancer patients with PALM received 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) intravenously on days 1-5, and intra-arterial infusion of etoposide (80 mg/m(2)) and oxaliplatin (80 mg/m(2)) on days 6 and 20, repeated 2 cycles. Patients achieved PR or CR of the para-aortic lymph node (PAL) were performed D2 dissection, followed by 6 cycles chemotherapy with XELOX regimen, oxaliplatin (130 mg/m(2)) on day 1 and xeloda (1000 mg/m(2)) on days 1 to 14 of a 28-day cycle, and radiotherapy to the region of PALM.. Forty-six patients completed 2 cycles of neoadjuvant chemotherapy. The overall response rate of the primary tumor was 80.4 % (37/46). The response rate of PAL was 76.1 % (35/46). Thirty-two patients underwent D2 dissection and six cases achieved pathological complete response (pCR). The toxicity profile was well tolerable and there was no treatment-related death. The median survival time for all patients was 23 months, and for nonsurgical and surgical patients were 12 and 29 months (p < 0.001), respectively. The 1-year, 2-year and 3-year survival rate was 70.96, 43.27 and 35.48 % for all patients, and for surgical patients was 96.875, 68.75, and 40.63 %.. Advanced gastric cancer patients with PALM can obtain a survival benefit from neoadjuvant chemotherapy, subsequent surgery and radiotherapy.. Current Controlled Trials ChiCTR-TRC-12002046 .

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Pilot Projects; Radiotherapy, Adjuvant; Stomach Neoplasms; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Sigmoid Neoplasms; Stomach Neoplasms

The prognosis of unresectable locally advanced gastric cancer is poor. We applied preoperative chemotherapy via intra-arterial and intravenous administration to convert an initially unresectable gastric cancer to a resectable cancer.. From January 2005 to December 2010, 105 patients with unresectable locally advanced gastric cancer (T3-4N1-3M0) were selected for preoperative chemotherapy with 5-FU + leucovorin + etoposide + oxaliplatin + epirubicin (FLEEOX) regimen. 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) were administered by intravenous infusion on days 1-5. Intra-arterial administration of etoposide (80 mg/m(2)), oxaliplatin (80 mg/m(2)), and epirubicin (30 mg/m(2)) was performed by Seldinger method on days 6 and 20, repeated two cycles. Patients who achieved partial response (PR) or complete response (CR) underwent D2 dissection, followed by four to six cycles of XELOX chemotherapy. The response rate, 1- and 3-year survival rate, and R0 resection rate were evaluated.. The response rate of preoperative chemotherapy was 78.1 % (82 of 105 patients), with 7 cases of CR and 75 cases of PR, respectively. After chemotherapy, a total of 78 patients (74.3 %) underwent surgery, and 67 cases achieved R0 resection (85.9 %). The 1- and 3-year overall survival (OS) rate of all 105 patients was 71.9 and 31.7 % (median survival time, 18 months). The 1- and 3-year OS rate among the 78 patients treated with chemotherapy plus surgery was 84.5 and 40 % (median survival time, 30 months). Patients treated with chemotherapy plus surgery had significantly longer OS times than patients who underwent chemotherapy alone (P < 0.01).. Patients with unresectable gastric cancer may obtain a survival benefit from preoperative chemotherapy via intra-arterial and intravenous administration and subsequent surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intra-Arterial; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Prognosis; Remission Induction; Stomach Neoplasms; Survival Rate

The insulin-like growth factor (IGF) axis plays a crucial role in proliferation, differentiation, migration, angiogenesis, and apoptosis. The present study evaluated the associations between IGF axis single-nucleotide polymorphisms (SNPs) and clinical outcomes in advanced gastric cancer (AGC) patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). A total of 190 patients undergoing FOLFOX chemotherapy for AGC were considered eligible for this study. Forty-four SNPs of 10 IGF axis genes were genotyped. Levels of serum IGF1 were measured using enzyme-linked immunoassays. SNPs of the IGF1R (rs12423791), and IGF1 (rs2162679, rs5742612, rs35767) genes were significantly associated with tumor response to FOLFOX. SNPs of rs4619 and rs17847203 were significantly associated with PFS (hazard ratio [HR] 0.575, 95% CI 0.385-0.858, P = 0.007; and HR 2.530, 95% CI 1.289-4.966, P = 0.007; respectively). SNPs of rs2872060 were significantly associated with OS-OS was shorter in patients carrying the TT variant than in those with the GG/GT genotypes (HR, 1.708, 95% CI 1.024-2.850, P = 0.040). The GT genotype of rs12847203 was also identified as an independent prognostic factor (HR 2.087, 95% CI 1.070-4.069, P = 0.031). These results suggest that IGF axis-pathway SNPs could be used as prognostic biomarkers of the outcome of FOLFOX chemotherapy in AGC patients. This information may facilitate identification of population subgroups that could benefit from IGF1R-targeted agents.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Insulin-Like Growth Factor I; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Oxaliplatin; Polymorphism, Single Nucleotide; Receptor, IGF Type 1; Receptors, Somatomedin; Stomach Neoplasms; Treatment Outcome; Young Adult

The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis.. Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result.. Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02).. IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Fluorouracil; Humans; Hyperthermia, Induced; Laparoscopy; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Peritoneal Neoplasms; Peritoneum; Stomach Neoplasms; Treatment Outcome

Use of perioperative chemotherapy had significantly improved prognosis of localized gastric cancer. Two studies have validated this approach using cisplatin based chemotherapy despite important toxicities. We conducted this study with the aim to evaluate efficacy and toxicity of FOLFOX regimen in this setting.. This is a retrospective study including patients followed for gastric cancer in the Oncology Department of the military hospital Mohamed V in Rabat, Morocco over a period of 7 years from 2007 to 2013. Patients received 4 cycles of mFOLFOX as perioperative regimen. Assessment of tumor response after completion of preoperative chemotherapy was granted by comparative CT scan, tumor markers measurements and R0 surgery rate.Adverse events were graded according to classification of the National Cancer Institute Common Toxicity Criteria version 4.0.. Thirty-one patients were included in this study. Use of preoperative chemotherapy showed partial response in fourteen patients (45.1%), stabilization in fifteen patients (48.4%). Tumor markers CEA and CA 19- 9 were significantly decreased. R0 resection rate was 83.87%. Only 2 (6.45%) cases of grade 3/4 hematologic toxicity were reported in our study. Achieving programmed postoperative chemotherapy was possible in 72.41% of patients.. Our study is limited by the retrospective design and small sample size but FOLFOX chemotherapy seems effective and well tolerated in this setting and its place deserves to be studied in a larger study.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Digestive System Surgical Procedures; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Perioperative Care; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.. IVIM-DWI was performed with 12 b-values (0-800 s/mm(2)) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D(*))] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD(*)%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed.. The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTVtreatment% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTVtreatment% = 29.07% ± 10.01% and ΔTVcontrol% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%treatment, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%control, median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7 (P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group (ΔD%treatment, median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group (ΔD%control, median -0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5 (P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up (median, -34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016; -50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008; -49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and -46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points (median, -32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008; -44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008; -59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and -47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis (r s = 0.720, P < 0.001; r s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D (r s = 0.626, P = 0.001; r s = 0.542, P = 0.005, respectively). Perfusion-related parameters (f and D(*)) were positively correlated to MVD (r s = 0.618, P = 0.001; r s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor (r s = -0.550, P = 0.004; r s = -0.692, P < 0.001, respectively).. IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Fluorouracil; Humans; Image Processing, Computer-Assisted; In Situ Nick-End Labeling; Leucovorin; Mice; Mice, Nude; Microvessels; Necrosis; Neoplasm Transplantation; Stomach Neoplasms; Transplantation, Heterologous; Xenograft Model Antitumor Assays

Gastric cancer is considered the fourth most common cancer and second most common cause of cancerrelated mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer.. To evaluate the responses and complications of FOLFOX4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer.. From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX4 regimen consisting of a 2h infusion of oxaliplatin 85 mg/m2 (day 1), continuous infusion of 1000mg/ m2 5Fu in 24h., and leucovorin 200 mg/m2 in 2h infusion as a firstline chemotherapy.. A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCICTC were seen.. The FOLFOX4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Neoplasm Staging; Organoplatinum Compounds; Prognosis; Remission Induction; Stomach Neoplasms; Survival Rate

Perioperative chemotherapy with 5-fluorouracil and cisplatin, with or without epirubicin, improves overall survival in resectable gastroesophageal junction and gastric adenocarcinoma. The aim of this retrospective multicenter study was to evaluate the safety and efficacy of perioperative chemotherapy with a FOLFOX-based regimen.. We enrolled patients with resectable gastric or gastroesophageal adenocarcinoma, who had at least 3 cycles of a pre-operative FOLFOX-based regimen. The primary end point was the feasibility of the peri-operative chemotherapy.. We enrolled 109 patients from 2007 to 2012 in 12 centres. Their median age was 66, 67% were men and 73% had gastric tumours. The median number of chemotherapy courses was 6 with a median of 4 pre-operative cycles and 2 post-operative cycles. Twenty-three patients received at least 8 cycles of chemotherapy. In univariate analysis, the Karnofsky index at inclusion was the only factor associated with 8 cycles of chemotherapy. An R0 resection was achieved in 100 patients (95.2%).. The FOLFOX-based perioperative regimen achieves favourable results in real life practice. The optimal number of chemotherapy cycle remains to be determined. FOLFOX regimen may be used as an alternative treatment option to a cisplatin-based regimen in resectable gastroesophageal adenocarcinoma. A prospective randomized trial is needed to confirm these results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Digestive System Surgical Procedures; Esophageal Neoplasms; Female; Fluorouracil; France; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Perioperative Period; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Survival Rate

Gastric cancer in pregnant women is rare. When physicians encounter a patient with pregnancy-associated gastric cancer, it is important to take a multidisciplinary approach and respect the will of the patient. We herein describe a case of gastric cancer during pregnancy.. A 36-year-old woman at 18 weeks of gestation was diagnosed with advanced gastric cancer. She underwent totally laparoscopic distal gastrectomy at 23 weeks of gestation and four cycles of FOLFOX6 without any severe toxicity. At 36 weeks of gestation, a healthy baby was born. After delivery, the patient was treated with additional chemotherapy. She has finished chemotherapy and has been followed-up without recurrence for 1 year after operation.. Laparoscopic gastrectomy followed by chemotherapy for gastric cancer during pregnancy might be a safe option.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastrectomy; Humans; Laparoscopy; Leucovorin; Neoplasm Recurrence, Local; Organoplatinum Compounds; Pregnancy; Pregnancy Complications, Neoplastic; Stomach Neoplasms

Although adjuvant chemoradiotherapy has been an important part in the treatment of gastric cancer, whether or not adjuvant radiation can benefit patients undergoing resection with D2 lymph node dissection remains controversial. This retrospective study aimed to evaluate the role of adjuvant chemoradiotherapy on patients with D2-resected gastric cancer. A total of 337 patients with resected gastric cancer treated at Zhongnan Hospital of Wuhan University from 2004 to 2012 were retrospectively analyzed. Eligible patients were divided into the adjuvant chemoradiotherapy group (CRT; n = 124) and the adjuvant chemotherapy group (CT; n = 213). The primary endpoints were disease-free survival (DFS) and overall survival (OS), with toxicity as the secondary endpoint. A subgroup analysis was performed based on clinical staging. The two groups were comparable in baseline characteristic, except for the number of lymph nodes dissected. The median OSs in the CRT and CT groups were 51.0 months and 48.6 months, respectively (P = 0.251), and the median DFSs were 40.7 months and 31.2 months, respectively (P = 0.112). Subgroup analysis revealed that the median OSs in patients at stage IIIc in the CRT group and CT group were 29.0 and 23.0 months, respectively (P = 0.049), and those of the median DFSs were 21.2 and 15.1 months, respectively (P = 0.015). There was no significant difference in main adverse events between two groups. Collectively, adjuvant chemoradiotherapy in gastric cancer patients with D2 resection was well tolerated. For Stage IIIc patients, the addition of adjuvant chemoradiotherapy was associated with a significant benefit in both OS and DFS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Young Adult

The aim of this study was to evaluate the activity of the combination of 5-fluorouracil/folinic acid and irinotecan (FOLFIRI) as third-line chemotherapy (CT) in metastatic gastric cancer (mGC) patients pretreated with platinum derivatives, fluoropyrimidines, and taxanes.. We prospectively collected data of mGC patients treated with third-line FOLFIRI at our institution from 2009 to 2014. Eligible patients should be treated with a fluoropyrimidine-platinum first-line CT and a subsequent taxane-based second-line CT. FOLFIRI consisted of irinotecan 180 mg/m2 and leucovorin 200 mg/m2, followed by 5-fluorouracil 2,800 mg/m2 (administered as 48-hour i.v. continuous infusion from day 1 to 3), with cycles repeated every 2 weeks. Response rate (RR) was evaluated according to RECIST version 1.0, while progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.. A total of 33 patients were included. The majority (97%) had good performance status (0-1 according to ECOG), while median PFS after first-line and second-line CT was 5.2 and 4.4 months, respectively. Two patients experienced an objective response (RR: 6%), while 14 patients achieved disease stabilization (disease control rate: 42%). Median PFS and OS from the start of third-line CT were 3.3 and 7.5 months, respectively. Hematological and nonhematological grade 3-4 toxicities were uncommon and included neutropenia (6.1%), diarrhea (9.1%), vomiting (3%), and asthenia (3%). Febrile neutropenia was not reported.. Third-line CT with FOLFIRI may be an option in heavily pretreated mGC patients with preserved performance status and organ function. This regimen has a favorable safety profile, and signs of activity have been observed after standard first- and second-line CT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Camptothecin; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neutropenia; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Retreatment; Stomach Neoplasms; Survival Rate; Vomiting; White People

Advanced gastric cancer patients with malignant ascites cannot tolerate S-1 plus cisplatin-containing therapy. The good toxicity profile of the FLTAX regimen(5-fluorouracil[5-FU]and Leucovorin[l-LV]combined with weekly paclitaxel) might make it a viable alternative treatment for these patients. We retrospectively evaluated the efficacy and safety of FLTAX in advanced gastric cancer patients.. Patients with advanced gastric cancer with malignant ascites were treated with 60mg/m2 paclitaxel, followed by 500 mg/m2 5-FU and 250 mg/m2 l-LV on days 1, 8, and 15. Treatment courses were repeated every 28 days. Patients were treated in our hospital from 2014 to 2016.. Three advanced gastric cancer patients with malignant ascites received the FLTAX regimen. The median age was 66 years(range 58-66). The median number of treatment courses was 2(range 1-20). The median progression-free survival and overall survival were 55(95%CI 24-.)and 272(95%CI 108-.)days, respectively. Observed Grade 3-4 adverse events were as follows: hyponatremia(1), anorexia(1), upper gastrointestinal hemorrhage(1), and thromboembolic event(1). No treatment-related death occurred.. FLTAX demonstrated an acceptable toxicity profile, and may be a good option for gastric cancer patients with malignant ascites.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Paclitaxel; Retrospective Studies; Stomach Neoplasms

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients.. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated.. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71-89) in the single regimen group (SG, 70 patients) and 73 years (range 71-81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85-5.95) and 4.1 months (95 % CI 2.62-5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17-9.08) and 7.6 months (95 % CI 5.50-9.69; P = 0.782), respectively. Hematologic (P < 0.001) and non-hematologic toxicities (P < 0.001) were more frequent in the CG. The most common causes of chemotherapy cessation were disease progression in the SG and decreased performance status in the CG.. Single-agent treatment should be considered a first-line palliative chemotherapy option for elderly patients with GC.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Organoplatinum Compounds; Oxonic Acid; Palliative Care; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Trastuzumab with 5-fluorouracil (5-FU) and cisplatin offers prolonged survival in patients with HER2-overexpressing advanced gastric cancer (AGC) and advanced gastro-oesophageal junction cancer (AGOJ). Oxaliplatin in combination with intravenous 5-FU plus leucovorin (LV; modified [m]FOLFOX6) or capecitabine (XELOX) improves tolerability compared with 5-FU/cisplatin regimen. There are few data available on the efficacy and safety of trastuzumab-oxaliplatin-based chemotherapy in previously untreated HER2-positive AGC and AGOJ patients.. Clinical data were retrospectively analysed in patients receiving trastuzumab plus mFOLFOX6 or XELOX as first-line therapy between July 2009 and December 2012. Eligible patients had histologically proven AGC or AGOJ, HER2 overexpression, and no prior chemotherapy for metastatic disease.. Thirty-four patients met the eligibility criteria. Median age was 63 years, 79% of patients had ECOG PS score of 0-1, and all had metastatic disease. Median duration of treatment was 7.5 months. Overall response rate was 41% (95% CI: 25-56). Median progression-free survival and overall survival were 9.0 months (95% CI: 5.6-12) and 17.3 months (95% CI: 13.5-32.3), respectively. Tolerability was acceptable. The most frequent grade 3-4 toxicities were neutropenia (8.8%) and neuropathy (17.6%).. mFOLFOX6-trastuzumab combination is an efficient regimen with an acceptable safety profile for AGC and AGOJ patients. These results warrant further prospective study.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaloacetates; Receptor, ErbB-2; Retrospective Studies; Stomach Neoplasms; Trastuzumab

Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS).. AGC patients receiving the mFOLFOX6 regimen including oxaliplatin 85 mg/m2, bolus of 5-FU 400 mg/m2 and LV 400 mg/m2 on the first day, followed by 2400mg/m2 of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study.. A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher.. In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Crystallization; Esophagitis; Esophagoscopy; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Rare Diseases; Risk Factors; Stomach Neoplasms

Genetic variability of DNA repair mechanisms influences chemotherapy treatment outcome of gastric cancer. We conducted a cohort study to investigate the role of ERCC1-ERCC2 gene polymorphisms in the chemotherapy response and clinic outcome of gastric cancer. Between March 2011 and March 2013, 228 gastric patients who were newly diagnosed with histopathology were enrolled in our study. Genotypes of ERCC1 rs11615, rs3212986, rs2298881 and ERCC2 rs3212986 were conducted by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. We found that individuals carrying TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 were associated with better response to chemotherapy and longer survival time of gastric cancer. Moreover, individuals with AA genotype of ERCC2 rs1799793 were correlated with shorter survival of gastric cancer. In conclusion, ERCC1 rs11615, rs2298881 and ERCC2 rs1799793 polymorphism play an important role in the treatment outcome of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease Progression; DNA Repair; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Gene Frequency; Genotype; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Phenotype; Polymorphism, Single Nucleotide; Proportional Hazards Models; Remission Induction; Risk Factors; Stomach Neoplasms; Time Factors; Treatment Outcome; Xeroderma Pigmentosum Group D Protein

In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme.. We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy.. Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %.. This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Esophagogastric Junction; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms

The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer.. Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0.. Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP.. FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS).. Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity.. Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%).. FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cognition; Cognition Disorders; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Immunosuppressive Agents; Infusions, Intravenous; Italy; Leucovorin; Maintenance Chemotherapy; Male; Organoplatinum Compounds; Psychometrics; Retrospective Studies; Stomach Neoplasms; Survival Rate; Time Factors; Treatment Outcome; Vitamin B Complex

A combination of platin-based perioperative chemotherapy (PBPC) plus surgical resection has become the standard of care in Europe for locally advanced esophagogastric adenocarcinoma (EGAC). In contrast to preoperative chemotherapy, the postoperative administration of chemotherapy is omitted in a high percentage of patients. We conducted this database study to analyse the impact of postoperative completion of perioperative chemotherapy on patient outcome.. Patients with EGAC (cT3-4 and/or cN+) were treated with preoperative PBPC plus curative surgical resection. Patient demographics, postoperative tumour stages, histopathological regression (HPR) and administration of postoperative chemotherapy were correlated with overall survival.. Of one-hundred-thirty-four patients, 76 received preoperative docetaxel, folinic acid, fluorouracil, oxaliplatin (FLOT), 53 patients epirubicin, cisplatin, folinic acid (ECF) and 5 epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy. The 5-year-survival for the whole collective was 58%. Designated postoperative chemotherapy was omitted in 36% of the patients. 5-year-survival was 75.8% in patients who received pre- and post-operative chemotherapy and 40.3% in patients with only preoperative chemotherapy (p < 0.001). Histopathological regression, postoperative nodal status and administration of postoperative chemotherapy were identified as independent prognostic factors. Analysis of subgroups revealed a pronounced survival benefit after administration of postoperative chemotherapy in patients with ypN+ stages (5-year-survival 64.5% vs 9.7%, p = 0.002) and poor HPR (5-year-survival 55.5% vs 19.3%, p = 0.015).. Our study provides further evidence that administration of postoperative chemotherapy may contribute to the achieved survival benefit of PBPC in patients with EGAC and implies a beneficial effect especially in presence of lymphonodular tumour involvement and limited HPR.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Databases, Factual; Docetaxel; Epirubicin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Postoperative Period; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Taxoids; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Stomach Neoplasms

Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colonoscopy; Female; Fluorouracil; Gastroscopy; Humans; Hyperplasia; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Positron-Emission Tomography; Stomach Neoplasms; Tomography, X-Ray Computed

We investigate whether three common polymorphisms in ERCC1 and ERCC2 are predictor factors for the chemotherapy response, as well as the clinic outcome of patients with gastric cancer. Between May 2011 and May 2013, 263 patients with gastric cancer who were newly diagnosed by histopathology were enrolled in our study. Genotyping of the ERCC1 rs11615 and rs3212986, and ERCC2 rs1799793 polymorphisms were conducted by the polymerase chain reaction-restriction fragment length polymorphism assay. Patients carrying the TT genotype and TT+CT genotype of ERCC1 rs11615 were associated with poorer response to chemotherapy and shorter survival times when compared with the CC genotype. In conclusion, our results suggested that the ERCC1 rs11615 polymorphism in the DNA repair pathways can be used as predictive factors to the clinical outcome of patients with gastric cancer.

Topics: Aged; Alleles; Antineoplastic Combined Chemotherapy Protocols; DNA Repair; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Genetic Variation; Genotype; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Treatment Outcome; Xeroderma Pigmentosum Group D Protein

To analyze the characteristics of recurrence in gastric cancer patients after radical gastrectomy and adjuvant chemotherapy.. The clinicopathological data of 110 gastric cancer patients who developed recurrence or second primary malignancies after radical gastrectomy and adjuvant chemotherapy with FOLFOX4 regimen or docetaxel plus FOLFOX4 regimen were analyzed retrospectively.. The median time to recurrence was 13.9 months (range, 1.7 to 63.1 months), and the median overall survival was 27.4 months (range, 6.9 to 90.7 months) in the whole group. The median survival time after recurrence was 10.1 months (range, 0.3 to 73.9 months). 82 (74.5%) patients had recurrence within 2 years after gastrectomy. The modes of surgical procedure and lymph node dissection influenced significantly on the time to recurrence (P<0.05 for both). Among the 110 patients with recurrence, 46 (41.8%) patients had peritoneal metastases, 33 (30.0%) had hematogenous metastases and 32 (29.1%) had locoregional lymph node metastases. Single, double, triple and quatro recurrences were observed at the first time of relapse in 78 (70.9%), 21(19.1%), 9(8.2%) and 2 cases (1.8%), respectively. Patients who developed simultaneous quatro recurrence had the poorest prognosis with a median overall survival of 15.2 months, significantly shorter than that of patients with single recurrence (31.8 months, P=0.003). Patients with peritoneal recurrence died most quickly ( mean 5.6 months), and patients with surgical field recurrence alone survived longest (mean 17.1 months).. Peritoneal, hematogenous and locoregional lymph node metastases are the most frequent recurrences after radical gastrectomy and adjuvant chemotherapy in patients with gastric cancer. Single recurrence occurred in most patients at the first relapse. Combination with other adjuvant treatments should be considered besides adjuvant chemotherapy in gastric cancer patients after radical gastrectomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Organoplatinum Compounds; Prognosis; Retrospective Studies; Stomach Neoplasms; Taxoids; Time Factors

Elucidation of the mechanisms by which gastric cancer cells acquire resistance to 5-fluorouracil (5FU) may provide important clues to the development of effective chemotherapy for 5FU-resistant gastric cancer. Four 5FU-resistant cell lines (MKN45/5FU, MKN74/5FU, NCI-N87/5FU, and KATOIII/5FU) were established by continuous exposure of the cells to progressively increasing concentrations of 5FU for about 1 year. Then, mRNA expression levels of four genes associated with 5FU metabolism, i.e., thymidylate synthase (TS), dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase, were quantitatively evaluated by real-time reverse transcriptase-polymerase chain reaction. In addition, TS protein expression was measured by Western blot analysis.. As compared with the parent cell lines, the 5FU-resistant cell lines showed 3.8- to 11.6-fold higher resistance to 5FU, as well as 1.9- to 3.5-fold higher TS mRNA expression and 1.6- to 7.1-fold higher TS protein expression. In contrast, the expressions of other genes did not differ significantly among the cell lines. The cytotoxicity of 5FU was enhanced 2.3- to 2.8 fold by leucovorin (LV) against three of the four 5FU-resistant cell lines.. Collectively, LV enhanced the cytotoxicity of 5FU not only against the parent gastric cancer cell lines, but also against the 5FU-resistant cell lines, even those with elevated TS expression levels. These results suggest that clinical studies of a combination of 5FU and LV are warranted in patients who have recurrent gastric cancer after 5FU-based therapy.

Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Stomach Neoplasms; Thymidylate Synthase; Up-Regulation

Docetaxel-cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC.. Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m(2)), oxaliplatin (85 mg/m(2)), and leucovorin (40 mg/m(2)) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m(2)) every 2 weeks.. Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %).. TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.. Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.. A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.. A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; DNA Repair; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Genotype; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Stomach Neoplasms

In a retrospective study we analyzed the impact of neoadjuvant chemotherapy (CTx) with the PELF - protocol (Cisplatin, Epirubicin, Leukovorin, 5-Fluoruracil) on mortality, recurrence and prognosis of patients with advanced gastric carcinoma, UICC stages Ib-III.. 64 patients were included. 26 patients received neoadjuvant CTx followed by surgical resection, 38 received surgical resection only. Tumor staging was performed by endoscopy, endosonography, computed tomography and laparoscopy. Patients staged Ib - III received two cycles of CTx according to the PELF-protocol. Adjuvant chemotherapy was not performed at all.. Complete (CR) or partial response (PR) was seen in 20 patients (77%), 19% showing CR and 58% PR. No benefit was observed in 6 patients (23%). Two of these 6 patients displayed tumor progression during CTx. Major toxicity was defined as grade 3 to 4 neutropenia or gastrointestinal side effects. One patient died under CTx because of neutropenia and was excluded from the overall patient collective. The curative resection rate was 77% after CTx and 74% after surgery only. The perioperative morbidity rate after CTx was 39% versus 66% after resection only. Recurrence rate after CTx was 38% and 61% after surgery alone; we detected an effective reduction of locoregional recurrence (12% vs. 26%). The overall survival was 38% after CTx and 42% after resection only. The 5-year survival rates were 45% in responders, 20% in non - responders and 42% in only resected patients. A subgroup analysis indicates that responders with stage III tumors may benefit with respect to their 5-year survival in comparable patients without neoadjuvant CTx. As to be expected, non-responders with stage III tumors did not benefit with respect to their survival. The 5-year-survival was approximated using a Kaplan-Meier curve and compared using a log-rank test.. In patients with advanced gastric carcinoma, neoadjuvant CTx with the PELF- protocol significantly reduces the recurrence rate, especially locoregionally, compared to surgery alone. In our study, there was no overall survival benefit after a 5-year follow-up period. Alone a subgroup of patients with stage III tumors appear to benefit significantly in the long term from neoadjuvant CTx.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Basaloid squamous cell carcinoma (BSCC) is a high-grade variant of squamous cell carcinoma usually localized in the aerodigestive tract, with a poor prognosis. Surgical resection is generally recommended, even if no standard treatment has been established yet.. Here, we report the case history of a patient diagnosed with BSCC at the esophagogastric junction who was successfully treated with chemotherapy alone, leading to a durable complete response.. The presented case illustrates the diagnostic challenges associated with BSCC of the esophagus and reports an unexpected chemosensitivity of this histotype to the combination of a platinum salt plus 5-fluorouracil, which could represent an optimal treatment strategy in unfit patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rare Diseases; Stomach Neoplasms; Treatment Outcome

To explore the efficacies of neoadjuvant chemotherapy plus nutritional supports for gastric cancer complicated with pyloric obstruction.. Retrospective analyses were performed for a total of 116 patients of gastric cancer complicated with pyloric obstruction undergoing exploratory laparotomy from January 2004 to June 2013.. Sixty-two patients (group A) received neoadjuvant chemotherapy (regimen of FOLFOX) plus preoperative nutritional support. And parenteral (PN, n = 30) and enteral (EN, n = 32) nutritional supports were provided. Another 54 patients (group B) underwent exploratory laparotomy alone. The serum level of albumin and score of quality of life in group A at the last preoperative day improved significantly. And EN was better than PN. The rate of excision/radical excision of group A (85.5%, 45.2%) was much higher than group B (64.8%, 18.5%) (both P < 0.05).. Nutritional support, especially EN, can improve the nutritional status and quality of life in patients with gastric cancer complicated with pyloric obstruction. And nutritional support plus neoadjuvant chemotherapy increase the rate of tumor excision.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastric Outlet Obstruction; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Nutritional Support; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

Breast cancer susceptibility gene 1 (BRCA1) expression differentially affects outcome to platinum- and taxane-based chemotherapy. Mediator of DNA damage checkpoint protein 1 (MDC1), p53-binding protein 1 (53BP1), multiple myeloma SET domain (MMSET) and ubiquitin-conjugating enzyme 9 (UBC9) are involved in DNA repair and could modify the BRCA1 predictive model.. Mediator of DNA damage checkpoint protein 1, 53BP1, MMSET and UBC9 mRNA were assessed in gastric tumours from patients in whom BRCA1 levels had previously been determined.. In vitro chemosensitivity assay, MMSET levels were higher in docetaxel-sensitive samples. In a separate cohort, survival was longer in those with low MMSET (12.3 vs 8.8 months; P=0.04) or UBC9 (12.4 vs 8.8 months; P=0.01) in patients receiving only folinic acid, fluorouracil (5-FU) and oxaliplatin (FOLFOX). Conversely, among patients receiving second-line docetaxel, longer survival was associated with high MMSET (19.1 vs 13.9 months; P=0.003). Patients with high MMSET and BRCA1 attained a median survival of 36.6 months, compared with 13.9 months for those with high BRCA1 and low MMSET (P=0.003). In the multivariate analyses, low MMSET (hazard ratio (HR), 0.59; P=0.04) and low UBC9 (HR, 0.52; P=0.01) levels were markers of longer survival to first-line FOLFOX, whereas palliative surgery (HR, 2.47; P=0.005), low BRCA1 (HR, 3.17; P=0.001) and low MMSET (HR, 2.52; P=0.004) levels were markers of shorter survival to second-line docetaxel.. Breast cancer susceptibility gene 1, MMSET and UBC9 can be useful for customising chemotherapy in gastric cancer patients.

Topics: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; BRCA1 Protein; Cell Cycle Proteins; Docetaxel; Female; Fluorouracil; Gene Expression; Histone-Lysine N-Methyltransferase; Humans; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nuclear Proteins; Organoplatinum Compounds; Proportional Hazards Models; Repressor Proteins; RNA, Messenger; Stomach Neoplasms; Taxoids; Trans-Activators; Tumor Suppressor p53-Binding Protein 1; Ubiquitin-Conjugating Enzymes; Young Adult

With improved chemotherapeutic regimens, metastasized gastric cancer may show a good response rendering an initially unresectable tumor resectable. We performed a retrospective analysis on the outcome of stage IV gastric cancer patients treated by chemotherapy followed by oncologic resection in a western institution.. From August 1988 to December 2010, a total number of 1,817 patients underwent surgery for gastric cancer at the Department of Surgery, Technical University of Munich. A retrospective analysis of our prospective gastric cancer database identified 58 patients with stage IV gastric cancer having undergone induction chemotherapy followed by surgery in an individualized treatment concept. After induction chemotherapy usually consisting of 2 cycles of PLF (cisplatin, 5-fluorouracil, leucovorin), resection was performed with or without removal of metastases in patients without disease progression. Patients were followed up until death or loss to follow up.. The three most common metastatic locations were liver (27.6 %), distant lymph nodes (22.4 %), and peritoneum (19.0 %). Of patients, 13.8 % had metastases in more than one location. Thirty-day mortality was 5.2 %, 90-day mortality was 13.8 %, while overall postoperative morbidity accounted for 24 %. In 19 (32.8 %) patients, a complete resection without any macroscopic tumor residues was achieved. In 39 (67.2 %) patients, tumors could not be completely removed with either local residual disease or residual disease at distant sites. Overall median survival was 20 months, while patients without residual tumor survived significantly longer (72 months) than patients with residual disease (12 months, p = 0.001).. Secondary surgery of metastasized gastric cancer may be justified in selected cases without progression under induction chemotherapy. An achievable complete removal of the primary tumor and metastases appears the main selection criterion for patients benefitting from this approach.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Gastrectomy; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Stomach Neoplasms; Treatment Outcome; Vitamin B Complex

Gastric cancer is one of the most lethal tumors in the Chilean population.. To report the results of adjuvant chemoradiotherapy in advanced gastric cancer.. Review of medical records of patients with locoregionally advanced gastric cancer, subjected to a curative resection and treated with adjuvant chemoradiotherapy. The treatment was based on the INT 0116/SWOG protocol, which includes 5-fuorouracil as a single agent. Patients were followed for a median of 58 months.. the records of 168 patients (99 men) treated between 2004 and 2011, were reviewed. Median survival was 41 months. Median lapses between surgery and onset of chemo and radiotherapy were 12 and 17 weeks, respectively. Overall three and five years survival was 53 and 41%, respectively. On multivariate analysis the factors associated with a lower survival were an antral location of the tumor, presence of signet ring cells and more than 15 involved lymph nodes.. Three and five years survival of gastric cancer patients subjected to adjuvant chemoradiotherapy was 53 and 41% respectively. These results are similar to those reported elsewhere.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Prognosis; Retrospective Studies; Stomach Neoplasms; Treatment Outcome; Vitamin B Complex; Young Adult

Gastric cancer is often diagnosed in advanced stage. Palliative chemotherapy or best supportive care is recommended for patients with metastatic gastric patients. In several clinical trials, palliative chemotherapy improved overall survival (OS) and progression-free survival (PFS), but the survival benefit of second-line chemotherapy was demonstrated in small cohort studies. The main aim of our study was to compare retrospectively the efficacy of second-line modified EOX (epirubicin, oxaliplatin and capecitabine) [mEOX] and irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) regimens in metastatic gastric cancer patients that progressed on first-line modified docetaxel-cisplatin-fluorouracil (DCF) regimen. Metastatic gastric cancer patients who progressed on modified DCF regimens were included. A total 105 patients were included to this study; 55 and 50 patients were treated with mEOX and FOLFIRI regimens, respectively. The clinicopathological and demographic characteristics of all patients were collected from the medical charts. Kaplan-Meier survival analysis was carried out for PFS and OS. The median follow-up of our study was 16 (4-85) months. In both groups, all of the patients were treated with first-line mDCF. Median cycle of second-line chemotherapy was 3 (1-8) and 3.5 (1-6) in EOX and FOLFIRI groups, respectively (P = 0.44). Overall response rate was observed in 34.6 % and 42.0 % of patients second-line chemotherapy in mEOX and FOLFIRI arms, respectively (P = 0.17). Median PFS was 5.5 and 6.3 months in mEOX and FOLFIRI arms, respectively (P = 0.98). Median OS was 6.9 and 7.0 months in mEOX and FOLFIRI arms, respectively, from the time of beginning second-line chemotherapy protocol (P = 0.89). As compared with FOLFIRI regimen, mEOX regimen was associated with less neutropenia, thrombocytopenia and anemia. Dose reduction and dose delay were significantly higher in FOLFIRI group compared to mEOX group (P < 0.001). In our trial, triplet regimens mEOX and FOLFIRI regimens have similar efficacy as second-line treatment for patients with metastatic gastric cancer. FOLFIRI regimen was associated with more hematological toxicity.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Febrile Neutropenia; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC).. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared.. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0-49) versus 13 (3-40)) between the two groups (P > 0.05). The number of lymph node metastases in the neoadjuvant group (3 (0-14)) was significantly fewer than that in the adjuvant group (6 (0-27)) (P = 0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P = 0.015).. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Treatment Outcome; Young Adult

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Stomach Neoplasms

Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient's OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dendritic Cells; Female; Fluorouracil; Forkhead Transcription Factors; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Leucovorin; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Prognosis; Proportional Hazards Models; Stomach Neoplasms; T-Lymphocytes, Regulatory

Postoperative chemoradiotherapy is accepted as standard treatment for stage IB-IV, M0 gastric cancer. Radiotherapy (RT) planning of gastric cancer is important because of the low radiation tolerance of surrounding critical organs. The purpose of this study was to compare the dosimetric aspects of 2-dimensional (2D) and 3-dimensional (3D) treatment plans, with the twin aims of evaluating the adequacy of 2D planning fields on coverage of planning target volume (PTV) and 3D conformal plans for both covering PTV and reducing the normal tissue doses.. Thirty-six patients with stage II-IV gastric adenocarcinoma were treated with adjuvant chemoradiotherapy using 3DRT. For each patient, a second 2D treatment plan was generated. The two techniques were compared for target volume coverage and dose to normal tissues using dose volume histogram (DVH) analysis.. 3DRT provides more adequate coverage of the target volume. Comparative DVHs for the left kidney and spinal cord demonstrate lower radiation doses with the 3D technique.. 3DRT produced better dose distributions and reduced radiation doses to left kidney and spinal cord compared to the 2D technique. For this reason it can be predicted that 3DRT will result in better tumor control and less normal tissue complications.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Fluorouracil; Gastrectomy; Humans; Imaging, Three-Dimensional; Leucovorin; Neoplasm Staging; Organs at Risk; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed; Vitamin B Complex

This observational study compares the effect of different radiotherapy techniques on late nephrotoxicity after postoperative chemoradiotherapy for gastric cancer.. Dosimetric parameters were compared between AP-PA, 3D-conformal and IMRT techniques. Renal function was measured by (99m)Tc-MAG-3 renography, glomerular filtration rate (GFR) and the development of hypertension. Mixed effects models were used to compare renal function over time.. Eighty-seven patients treated between 2002 and 2010 were included, AP-PA (n=31), 3D-conformal (n=25) and IMRT (n=31), all 45 Gy in 25 fractions. Concurrent chemotherapy: 5FU/leucovorin (n=4), capecitabine (n=37), and capecitabine/cisplatin (n=46). Median follow-up time was 4.7 years (range 0.2-8). With IMRT, the mean dose to the left kidney was significantly lower. Left kidney function decreased progressively in the total study population, however with IMRT this occurred at a lower rate. A dose-effect relationship was present between mean dose to the left kidney and the left kidney function. GFR decreased only moderately in time, which was not different between techniques. Six patients developed hypertension, of whom none in the IMRT group.. This study confirms progressive late nephrotoxicity in patients treated with postoperative chemoradiotherapy by different techniques for gastric cancer. Nephrotoxicity was less severe with IMRT and should be considered the preferred technique.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Cisplatin; Deoxycytidine; Female; Fluorouracil; Humans; Kidney; Kidney Diseases; Leucovorin; Male; Middle Aged; Radiation Injuries; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Stomach Neoplasms

We retrospectively analyzed the feasibility and adverse events for two regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5-FU/LV) compared to S-1 in D2-resected gastric cancer patients.. The study included 405 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection and received adjuvant therapy between January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1 regimens were analyzed.. Out of the 405 patients, 244 (60.2%) had CRT and 161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences of the physician and the patient. S-1 was more frequently administered to patients with older age (age≥70) and those with early-stage disease (stage II). The stage was significantly more advanced in the CRT group compared to the S-1 group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%, respectively; p<0.001). The completion rate of the planned therapy was significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%, respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7% vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%, respectively; p=0.034) were significantly more frequent in the CRT cohort compared to the S-1 group.. Both adjuvant CRT with 5-FU/LV and adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients. Patients with old age or early stage disease tend to prefer S-1 therapy to chemoradiation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

To explore the feasibility of short-term neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (AGC), and to compare clinical efficacy of short-term neoadjuvant chemotherapy with different ways.. Clinical data of 310 AGC patients treated with one course of NACT using EOF regimen(epirubicin, oxaliplatin and fluorouracil plus calcium folinate) in our hospital from January 2008 to December 2011 were retrospectively analyzes. Efficacy was compared between regional arterial infusion chemotherapy and intravenously chemotherapy.. All the 310 AGC patients completed one course of NACT and none was interrupted by adverse events. Postoperative pathological remission rate was 33.9% (105/310) and 5 patients (1.6%) had complete pathological remission. The pathologic response rate in the regional arterial infusion chemotherapy group was higher than that in the intravenously chemotherapy group(42.4% vs. 23.6%, P = 0.001). Multivariate analysis revealed that chemotherapy method(HR=1.827, 95% CI:1.006-3.316, P = 0.048) was associated with significantly higher pathologic response.. Pathological response rate is quite low following short-term NACT. Regional arterial infusion chemotherapy with short-term NACT can improve the pathological response rate of advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Epirubicin; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Retrospective Studies; Stomach Neoplasms

In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4(carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer.. A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy.. Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA >50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had a positive prediction value for pathologic response to neoadjuvant chemotherapy according to the ROC curve (AUC: 0.764, 95% CI: 0.584 to 0.945, P = 0.020).. Our results suggest that high preoperative serum levels of CA72-4 and CA19-9 are associated with higher risk of death, high pretreatment CEA levels (>50 ng/ml) may predict clinical disease progression after neoadjuvant chemotherapy, and a decrease (>70%) of CA72-4 may predict pathologic response to neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection.. Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered.. A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated.. Cisplatin HIPEC combined with paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Hyperthermia, Induced; Infusions, Intravenous; Infusions, Parenteral; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Stomach Neoplasms; Time Factors; Treatment Outcome

The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer.. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2.. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival.. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Docetaxel; Drug Administration Schedule; Female; Fluorouracil; Humans; Hypothermia, Induced; Infusions, Parenteral; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Taxoids; Time Factors; Treatment Outcome

To evaluate the role of endoscopic ultrasound (EUS) in restaging and predicting response after neoadjuvant chemotherapy in patients with advanced gastric cancer.. In all, 48 advanced gastric cancer patients were recruited from June 2007 to December 2010 after providing their written, informed consent. All patients underwent an EUS before and after three cycles of neoadjuvant chemotherapy (FOLFOX 6), and then a radical resection was performed 3-4 weeks after chemotherapy. The results of EUS were compared to the pathological results of the resected specimens.. After chemotherapy, the overall sensitivity of EUS for T classification was 63 percent (T2: 44%, T3: 68%, T4: 90%), and overstaging (31%) was more frequent than understaging (6%). The sensitivity and specificity of EUS for N classification were 56 and 50 percent, respectively (N0: without lymph node metastasis, N1: with lymph node metastasis), with 15 percent overstaged and 32% understaged. EUS revealed that T and/or N downstaging occurred in 46 percent (22/48) of patients after chemotherapy, most of whom had a favorable pathological response to the chemotherapy compared with other patients without T and/or N downstaging. No T or N upstaging was observed after neoadjuvant chemotherapy.. The accuracy of restaging by EUS for T and N classification was not as good as pathological data for locally advanced gastric cancer patients after neoadjuvant chemotherapy. However, T and/or N downstaging confirmed by EUS correlated well with the degree of pathological response to chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Endosonography; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Stomach Neoplasms

The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis.. A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles).. The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS.. Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Epirubicin; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms

Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen).. Chemotherapy-naive patients with metastatic gastric cancer (MGC) received D 60 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/m2/46 h continuous infusion) every 3 weeks. The primary endpoint was response rate.. One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%).. Low-dose DC- De Gramont regimen is active in MGC with a tolerable toxicity profile.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Disease-Free Survival; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Taxoids; Treatment Outcome

To investigate the predictive value of seven gastric cancer-associated factors on neoadjuvant chemotherapy in patients with advanced gastric cancer.. Expressions of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII were detected by immunohistochemistry in gastric cancer tissues of 53 cases before and after mFOLFOX7 neoadjuvant chemotherapy. Chemotherapy efficacy was evaluated according to RECIST 1.1 standard combined with histopathology, and the relationship between various genes and chemotherapy efficacy was analyzed by univariate and logistic multivariate regression analyses.. The clinical response rate was 52.8% (28/53) in neoadjuvant chemotherapy, including complete response in none, partial response in 28 cases (52.8%), stable disease in 24 cases (45.3%) and progressive disease in 1 case (1.9%). The expressions of all the genes were not significantly different before and after neoadjuvant chemotherapy (P>0.05). Neoadjuvant chemotherapy efficacy was 83.3% (10/12) in the patients of HER2 positive expression and 43.9% (18/41) in the patients of HER2 negative expression. The former was significant higher than the latter (P=0.016). Response rate of patients with P53 positive expression was 35.7% (10/28), significantly lower than 72.0% (18/25) of those with P53 negative expression (P=0.008). Six patients with both HER2 positive expression and P53 negative expression showed better efficacy. The expressions of C-met, EGFR, Ki-67, MMP7 and TOPOII were not associated with response to neoadjuvant chemotherapy (P>0.05). HER2 and P53 were independent influencing factors of neoadjuvant chemotherapy (P<0.05).. Expressions of HER2 and P53 have great value in the prediction of mFOLFOX7 neoadjuvant chemotherapy efficacy, suggesting that as independent factors, HER2 and P53 may be used to predict the efficacy before chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Receptor, ErbB-2; Stomach Neoplasms; Treatment Outcome; Tumor Suppressor Protein p53

To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection.. Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matched-pair analyses.. Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018).. Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; China; Deoxycytidine; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Oxaloacetates; Propensity Score; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Time Factors; Treatment Outcome; Young Adult

We present the clinical observation of combined treatment of a patient with metastatic gastric cancer. The patient underwent combined chemotherapy for initially inoperable gastric cancer with metastases to the liver, paragastric lymph nodes, and peritoneal carcinomatosis with complete regression of distant metastases, which allowed radical surgery. The patient is currently under regular team observation without signs of disease. His present survival is 44 months.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Induction Chemotherapy; Leucovorin; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Treatment Outcome

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC). Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP) level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Fluorouracil; Gastroscopy; Humans; Leucovorin; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Recurrence; Silicates; Stomach Neoplasms; Titanium; Tomography, X-Ray Computed

Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX).. The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy.. NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS.. This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Organoplatinum Compounds; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Young Adult

Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer patients in the USA. However, in countries where D2 lymph node dissection is performed, the effect of radiotherapy on locoregional recurrence is controversial. The aim of this study is to compare the outcomes in pN3 gastric cancer patients following two adjuvant treatment modalities: chemotherapy (CT) and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer patients who underwent D2 lymph node dissection and had pTanyN3M0 stage (according to AJCC 6th edition) were identified. Fifty-three patients were treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during radiotherapy. For the CT arm, treatment protocols consisted of combination therapies involving FU and cisplatin as the backbone. Median overall survival (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15-37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT, respectively). Locoregional recurrence rates were also similar (p = 0.63). Only metastatic/dissected lymph node ratio (≥0.75) was identified as a prognostic factor in both univariate and multivariate analyses for DFS. Comparison of CT versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did not reveal any statistically significant difference in survival rates and locoregional recurrence.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Radiography; Radiotherapy, Adjuvant; Retrospective Studies; Stomach Neoplasms; Survival Rate

To determine the prognostic role of selected microRNA (miRNA) polymorphisms in advanced gastric cancer (AGC).. Six hundred and seventy-four AGC patients received 5-fluorouracil (F), leucovorin (L), oxaliplatin (O) or FL + cisplatin (P) or additional docetaxel (T) to FLO (FLOT) within four clinical trials. Polymorphisms of mir-26a1 (rs7372209), mir-27a (rs895819), mir-100 (rs1834306), mir-146a (rs2910164), mir-196-a2 (rs11614913), mir-219-1 (rs107822) and mir-423 (rs6505162) were genotyped. Variable selection for the final multivariate model (n = 487) was based on univariate and multivariate Cox-regression analyses with a cut-off P-value of ≤ 20%.. Genetic factors significantly associated with overall survival (OS) were rs7372209 (mir-26a1) variant genotypes (hazard ratio, HR 1.307 [95% confidence interval (CI) 1.031-1.656], P = 0.0272), rs895819 (mir-27a) variant genotypes (HR 1.304 [95% CI 1.031-1.650], P = 0.0270) and rs11614913 (mir-196a2) variant genotypes (HR 0.791 [95% CI 0.625-1.000], P = 0.0497). Clinical factors with significant impact on OS were Eastern Cooperative Oncology Group (ECOG) 2 performance status (HR 1.880 [95% CI 1.254-2.820], P = 0.0023), curative surgery of advanced disease (HR 0.235 [95% CI 0.123-0.449], P < 0.0001) and addition of docetaxel in locally AGC patients (HR 0.348 [95% CI 0.145-0.838], P = 0.0301). Combined analyses revealed an improved OS in patients without any unfavourable genotype of 18 months compared with 14, 12 and 10 months in patients with 1, 2 and 3 unfavourable genotypes, respectively (P = 0.0257).. These data suggest a significant impact of selected miRNA polymorphisms on prognosis in AGC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Female; Fluorouracil; Genetic Predisposition to Disease; Genotype; Humans; Leucovorin; Male; MicroRNAs; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Polymorphism, Single Nucleotide; Prognosis; Stomach Neoplasms; Survival; Taxoids; Vitamin B Complex; Young Adult

To observe the effect of curcumin combined folinic acid fluorouracil oxaliplatin (FOLFOX) on the gastric adenocarcinoma cell line BGC-823 and to explore its possible mechanisms.. Cells were divided into five groups, i.e. the blank control group, the curcumin group, the FOLFOX group (0.1 mmol/L 5-FU +5 micromol/L oxaliplatin), and the curcumin combined FOLFOX group. CCK-8 was used to detect cell activity. The cell apoptosis was observed using Hoechst dyeing. Caspase-3 test kit was applied to test Caspase-3 vitality. The mRNA expressions of Bcl-2 and Bax were detected by real time fluorescent quantitative PCR. The expressions of Bcl-2 and Bax protein were determined by Western blot.. The BGC-823 cells' proliferation could be inhibited, apoptosis induced, the Caspase-3 activity increased, expressions of Bcl-2 mRNA and Bcl-2 protein lowered, while Bax mRNA and Bax protein expressions increased in each medicated group. Besides, the efficacy of the curcumin combined FOLFOX group was superior to that of the curcumin group and the FOLFOX group, showing statistical difference (P < 0.01).. Curcumin combined FOLFOX could significantly inhibit the proliferation of BGC-823 cells possibly via promoting Bax expression and Caspase-3 activity, inhibiting Bcl-2 expression, thus inducing apoptosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Line, Tumor; Cell Proliferation; Curcumin; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms

To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.. Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to December 2006, were analyzed retrospectively. Patients with pT4 stage or distant metastasis were excluded. We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features, such as age, tumor size, tumor location and depth of invasion. At the same time, the relationship between postoperative chemotherapy and the 5-year survival rate among different subgroups were also analyzed.. The overall 5-year survival rate of the entire cohort was 63.7%. The 5-year survival rate was poor in those patients who were: (1) more than 65 years old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper portion of the stomach; and (4) with pT3 tumor. The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor (P = 0.019), but not in other subgroups. Moreover, there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups (P > 0.05).. For gastric cancer patients without lymph node metastasis, extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor. However, there was no evidence of a survival benefit from postoperative chemotherapy alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; China; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Postoperative Care; Retrospective Studies; Stomach Neoplasms; Vitamin B Complex; Young Adult

The role of second-line chemotherapy in advanced gastric cancer is not yet fully established.. We analysed 111 patients with advanced gastric cancer treated at the University Hospital Heidelberg (51) and the private oncology practice Bottrop/Dorsten (60) between 2001 and 2011, comparing the outcome of patients with first-line chemotherapy and those who received second-line chemotherapy.. Thirty-six patients were treated with one chemotherapy regimen, 75 patients received at least two different chemotherapies. Patients who received one chemotherapy regimen were older (median age 69 years) and had a shorter overall survival (6 months) than patients receiving sequential chemotherapies [median age 61 years, p = 0.009, overall survival 14 months (2-42), p = 0.001]. Under second-line chemotherapy, partial response was observed in 25 patients (33%) and stable disease for ≥3 months in 26 patients (35%). Patients treated before 2005 had a slightly better overall survival than patients treated in or after 2005. Survival was not influenced by the treatment centre (primary or tertiary), but was influenced by former surgery.. The prognosis of advanced gastric cancer is still poor. Selected patients may benefit from individualized salvage chemotherapy after failure of first-line chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Deoxycytidine; Docetaxel; Drug Administration Schedule; Epirubicin; Etoposide; Female; Fluorouracil; Gemcitabine; Germany; Hospitals, University; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prognosis; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Taxoids; Treatment Outcome

To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients.. A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed.. There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients.. It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Survival Rate

To explore an ideal method of digestive tract reconstruction and tolerance to adjuvant chemotherapy after radical proximal gastrectomy.. Thirty patients in the reconstruction group were treated by jejunal interposition, and other 30 patients received gastroesophagostomy (control group). The operation time, operation risk, occurrence of reflux esophagitis and postoperative 1-, 3-, 6-month nutrition statuses were evaluated. Forty-three patients received postoperative adjuvant chemotherapy with mFOLFOX-6 and tolerance to the chemotherapy was assessed.. The operation time of the reconstructional group was (162.2 ± 14.0)min and that of the control group was (137.6 ± 18.9)mi, with a statistically significant difference. (t = -5.7, P<0.01). There were no significant differences of operation risk, postoperative 2-, 4-, and 6-day C-reactive protein, 2-, 4- and 6-day systemic inflammatory response syndrome between the two groups. The differences of the occurrence of postoperative 1-, 3- and 6-month reflux esophagitis and 3- and 6-month nutritional status between the two groups were statistically significant. 18 of 19 (94.7%) patients in the reconstruction group completed all six cycles of chemotherapy, 24 patients in the control group received chemotherapy, and 12 (50.0%) of them completed 6 cycles of chemotherapy. There was a significant difference in the completion rate of chemotherapy of the two groups (P<0.05).. The postoperative complications of jejunal interposition are not inceased, the symptoms of reflux esophagitis are alleviated, the quality of life can be improved, and there is a better tolerance to adjuvant chemotherapy. Therefore, jejunal interposition after radical proximal gastrectomy is a rational method of digestive tract reconstruction.

Topics: Aged; Anastomosis, Surgical; Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Gastroesophageal Reflux; Humans; Jejunum; Leucovorin; Male; Middle Aged; Operative Time; Organoplatinum Compounds; Plastic Surgery Procedures; Quality of Life; Retrospective Studies; Stomach Neoplasms; Systemic Inflammatory Response Syndrome

The role of second-line therapy in gastric cancer patients mostly stemmed from clinical trials with monochemotherapy carried out in Asian countries. Nevertheless, these results cannot be broadly generalized as molecular studies suggested the existence of different sets of deregulated gene networks correlated with ethnicity. In the present study, we investigated the activity and safety of FOLFIRI given as a second-line therapy in metastatic gastric or gastro-esophageal junction cancer patients who experienced disease progression on or after first-line docetaxel-containing chemotherapy.. Patients with histologically confirmed metastatic gastric cancer who failed docetaxel-containing first-line therapy and who received FOLFIRI in second line were eligible for the study. Seventy patients treated at three Italian cancer centers between 2005 and 2012 entered the study. Patients received every 2 weeks irinotecan 180 mg/m2 as 1 h infusion on day 1, folinic acid 100 mg/m2 intravenously days 1-2, and fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 hours days 1-2.. We observed 1(1.4%) complete response, 15 (21.4%) partial response, for an overall response rate of 22.8% (95% confidence interval (CI): 13.4-32.3). Stable disease was recorded in 21 (30%) patients. Median progression-free survival and overall survival were 3.8 months (95% CI: 3.3-4.4) and 6.2 months (95% CI: 5.3-7.1), respectively. The treatment was well tolerated, as the most common G3-4 toxicities were neutropenia (28.5%) and diarrhea (14.5%).. FOLFIRI appears an effective and safe treatment option for pretreated metastatic gastric cancer patients, and deserves further investigation in randomized clinical trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cohort Studies; Disease Progression; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Taxoids

To evaluate potential protein markers for oxaliplatin-based first-line chemotherapy of metastatic gastric cancer (MGC), we have used proteomic analysis to compare the difference of serum proteomic spectra between responsive and non-responsive MGC patients.. Serum samples were collected before chemotherapy.Surface-enhanced laser desorption/ionisation time of-flight mass spectrometry (SELDI-TOF-MS) proteinchip array technology was applied to compare the differences of serous protein spectra between the twenty responsive patients and another fourteen non responsive patients. Cross validation was applied to identify the proper markers for an accurate judgment of prognosis.. Fifty proteins were picked out for significantly increased or decreased expression(p<0.05, Student t-test). Among them, sixteen protein masses with 1081, 1267, 2941, 2985, 3148, 3165,3199, 3219, 3249, 3281, 4182, 4390, 4482, 4509,4533 and 5001 m/z were chosen as components of the best proteomic biomarker pattern for judgment of chemotherapy prognosis in MGC patients, achieving a sensitivity of 95% (19/20) and a specificity of 78.6%(11/14), respectively.. SELDI-TOF-MS screens out the specific protein markers that help oncologists with judging the prognosis of oxaliplatin in combination with fluoropyrimidine, thus orientating first-line palliative chemotherapy for MGC patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Proteins; Organoplatinum Compounds; Oxaliplatin; Patient Selection; Precision Medicine; Predictive Value of Tests; Protein Array Analysis; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach Neoplasms; Time Factors; Treatment Outcome

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Radiotherapy Dosage; Retrospective Studies; Stomach Neoplasms; Survival Rate; Turkey; Young Adult

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) is an effective but highly toxic regimen for the treatment of advanced gastric cancer. To improve tolerability while maintaining the efficacy of the DCF regimen, we developed a modified DCF regimen including an infusional 5-fluorouracil administration according to the de Gramont regimen.. In this study, 70 patients with advanced gastric cancer were treated. Each 2-week cycle consisted of docetaxel (60 mg/m(2)), cisplatin (50 mg/m(2)), a 5-fluorouracil (400 mg/m(2)) i.v. bolus, and 5-fluorouracil (2,400 mg/m(2)) i.v. over 46 h plus leucovorin (400 mg/m(2)) i.v. over 2 h.. The median progression-free survival and overall survival were 9.0 months (95% CI, 7.1-10.9) and 10.8 months (95% CI, 7.4-14.2), respectively; the 1-year and 2-year overall survival rates were 46.3 and 18.4%, respectively. Twenty-nine (41.4%) partial responses, 19 (27.1%) stable disease, and 22 (31.4%) progression of disease were observed. Grade 3-4 toxicities included neutropenia (37.1%), febrile neutropenia (15.7%), thrombocytopenia (10.0%), anemia (8.6%), nausea and vomiting (10.0%), stomatitis (5.7%), infection (8.6%), and diarrhea (2.9%).. Our results show that a de Gramont-based DCF regimen may have tolerable toxicities and be an effective and convenient palliative treatment for advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Docetaxel; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

The development of ovarian metastases from gastric cancer indicates a turning point of the disease progression and is usually associated with poor prognosis. Efficacy of modern chemotherapy protocols in ovarian metastases from gastric cancer is unknown. In this case series, we have evaluated the chemosensitivity of ovarian metastases from gastric cancer in eight consecutive patients treated in our institution between January 2000 and April 2012. Median age at gastric cancer diagnosis was 48.3 years and ovarian metastases were mainly metachronous (88%). Patients were treated with FOLFOX or FOLFIRI protocols in first-line and with EOX protocol in second-line chemotherapy. These protocols of chemotherapy used in first- and second-line treatment were able to control the disease in 33.3% for ovarian metastases compared to 66.7% for extraovarian metastases. Mean overall survival (OS) from ovarian metastases diagnosis was 14.2 months. The four patients treated by bilateral oophorectomy had a longer mean OS (16 months) than the four patients who did not experienced surgery (12.3 months). In conclusion, this case series suggests that ovarian metastases from gastric cancer are less sensitive than extraovarian metastases to modern protocol of chemotherapy. To confirm these observations, a large retrospective study is ongoing.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy; Stomach Neoplasms

The aim of this study was to evaluate the activity and safety of the combination chemotherapy of 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI regimen) after failure of fluoropyrimidine, platinum, and taxane in gastric cancer (GC) and to evaluate the prognostic factors for survival.. Patients received biweekly FOLFIRI chemotherapy as third-line treatment. The FOLFIRI-1 consisted of irinotecan (180 mg/m(2) in a 2-h infusion) on day 1, and then leucovorin (200 mg/m(2) in a 2-h infusion) and 5-FU (a 400 mg/m(2) bolus, followed by 600 mg/m(2) in a 22-h continuous infusion) on days 1 and 2. FOLFIRI-2 consisted of irinotecan (180 mg/m(2) in a 2-h infusion) on day 1, and then leucovorin (400 mg/m(2) in a 2-h infusion) and 5-FU (a 400 mg/m(2) bolus, followed by 2400 mg/m(2) in a 46-h continuous infusion) on day 1.. A total of 158 patients were included. The overall response rate was 9.6 % in patients with measurable lesions. The median progression-free survival (PFS) and overall survival (OS) were 2.1 months [95 % confidence interval (CI), 1.7-2.5] and 5.6 months (95 % CI, 4.7-6.5), respectively. The major grade 3/4 toxicity was myelosuppression (36.7 %). Good performance status (PS), fewer metastatic sites, and longer duration from the first-line to third-line chemotherapy were independent prognostic factors affecting both PFS and OS.. The FOLFIRI regimen showed antitumor activity and tolerable toxicity profiles against advanced GC in the third-line setting. Patients with good PS, fewer metastatic sites and longer previous treatment duration might have the maximal benefit from third-line chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Camptothecin; Carcinoma, Signet Ring Cell; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Platinum; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

The multifunctional protein JWA was previously identified as a novel regulator of focal adhesion kinase (FAK/PTK2) in suppressing cancer cell adhesion, invasion and metastasis. JWA is downregulated in gastric cancer (GC) and a prognostic and predictive biomarker for resectable GC. However, the value of FAK combined with JWA for GC patients as a biomarker has not been studied. Here we evaluated the roles of FAK alone and combined with JWA in GC patients treated with surgery alone or combined with adjuvant platinum-based chemotherapy.. Two tissue microarrays were constructed of specimens from resected GC (n = 709 in total) for detection of FAK and JWA expression by immunohistochemistry. Correlations between both proteins and clinicopathological features as well as prognostic and predictive values were evaluated.. Compared with adjacent non-cancerous tissues, FAK protein levels were remarkably up-regulated in GC lesions (P < 0.001). High FAK alone or combined with low JWA expression significantly correlated with worse overall survival (OS) (both P < 0.001 in two cohorts). Simultaneously, JWA plus FAK expression was a more valuable prognostic biomarker than JWA or FAK alone. Moreover, the patients with high FAK only or combined with low JWA had significant benefit from adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) therapy compared with those with surgery alone (P = 0.003); however, the cases with adjuvant fluorouracil-leucovorin-cisplatin (FLP) therapy did not show these effects.. FAK plus JWA may serve as a more prognostic and predictive biomarker for GC than each separately with a potential clinical application.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Female; Fluorouracil; Focal Adhesion Kinase 2; Gastrectomy; Heat-Shock Proteins; Humans; Intracellular Signaling Peptides and Proteins; Leucovorin; Male; Membrane Transport Proteins; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms

3,4-Dihydroxy-L-phenylalanine decarboxylase (DDC) is an enzyme implicated in the biosynthetic pathways of the neurotransmitters dopamine and probably serotonin. DDC gene expression has been studied in numerous malignancies and the corresponding data have shown remarkable alterations in the mRNA and/or protein levels encoded by the gene. The aim of this study was to examine any modulations in the DDC mRNA levels in gastric cancer cells after their treatment with the chemotherapeutic agents 5-fluorouracil, leucovorin, irinotecan, etoposide, cisplatin, and taxol. The sensitivity of the AGS gastric adenocarcinoma cells to the antineoplastic drugs was evaluated using the MTT assay. Total RNA was extracted and reverse transcribed into cDNA. A highly sensitive quantitative real-time PCR methodology was developed for the quantification of DDC mRNA. GAPDH was used as a housekeeping gene. Relative quantification analysis was carried out using the comparative C T method ((Equation is included in full-text article.)). The treatment of AGS cells with several concentrations of various broadly used anticancer drugs resulted in significant modulations of the DDC mRNA levels compared with those in the untreated cells in a time-specific and drug-specific manner. Generally, DDC expression levels appeared to decrease after three time periods of exposure to the selected chemotherapeutic agents, suggesting a characteristic DDC mRNA expression profile that is possibly related to the mechanism of each drug. Our experimental data show that the DDC gene might serve as a new potential molecular biomarker predicting treatment response in gastric cancer cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Camptothecin; Cisplatin; Dopa Decarboxylase; Dose-Response Relationship, Drug; Etoposide; Fluorouracil; Gene Expression Regulation, Enzymologic; Humans; Irinotecan; Leucovorin; Paclitaxel; Real-Time Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms

Expression of MDM2 protein appears to be increased in malignancy and correlated to prognosis of tumors, but its role in gastric cancer remains controversial. Our recent investigations indicated that JWA was a novel candidate biomarker for gastric cancer. To evaluate the impact of MDM2 protein expression alone, and in combination with JWA, on the prognostic and predictive of patients with resectable gastric cancer, expression of MDM2 and JWA were examined by immunohistochemistry in three large cohorts (total n = 1131) of patient with gastric cancer. We found that MDM2 protein levels were significantly upregulated in gastric cancer (70.4%, 57 of 81) compared with adjacent non-cancerous tissues. High tumoral MDM2 expression significantly correlated with clinicopathologic characteristics, as well as with shorter overall survival (OS; P < 0.001 for all cohorts) in patients without adjuvant treatment. The effect of adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) in improving OS compared with surgery alone was evident only in the high MDM2 group (hazard ratio = 0.57; 95% confidence interval, 0.37-0.89; P = 0.013). Furthermore, knockdown of MDM2 and overexpression of JWA had a synergistic effect on suppression of gastric cancer cell proliferation and migration. Patients with low MDM2 and high JWA expression had a better outcome of survival compared with the other groups (P < 0.001 for all cohorts). For the first time, our data suggest that MDM2 is a potent prognostic and predictive factor for benefit from adjuvant fluorouracil-leucovorin-oxaliplatin chemotherapy in resectable gastric cancer. The combination of MDM2 expression and JWA could serve as a more effective candidate prognostic biomarker for gastric cancer.

Topics: Aged; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemotherapy, Adjuvant; Cohort Studies; Female; Fluorouracil; Heat-Shock Proteins; Humans; Intracellular Signaling Peptides and Proteins; Leucovorin; Male; Membrane Transport Proteins; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proto-Oncogene Proteins c-mdm2; Retrospective Studies; Stomach Neoplasms; Treatment Outcome; Up-Regulation

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Long QT Syndrome; Male; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Torsades de Pointes

The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).. Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.. Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).. Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chi-Square Distribution; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Female; Fluorouracil; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Phenotype; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Stomach Neoplasms; Time Factors; Treatment Outcome; Up-Regulation; Vascular Endothelial Growth Factor A; Young Adult

The aim of this study was to determine the pathological complete remission (pCR) rate, and its relationship to clinical outcome, in patients with adenocarcinoma of the stomach or oesophagogastric junction receiving preoperative 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) every 2 weeks. Data from these patients who received at least one cycle of preoperative FLOT followed by surgery were prospectively collected in three German centres. Outcome analyses were conducted and tumour samples were evaluated for pathological remission by a central pathologist. A total of 46 patients were included in this analysis. All patients had clinical T3- and/or N+-stages and 11 (23.9%) had distant metastases (M1). After a median of 4 (range 2-8) preoperative cycles, 8 of 46 patients (17.4%) achieved a pCR. The pCR rate was highest in tumours of intestinal type histology (30.8%) and in those located in the oesophagogastric junction (30.4%) and lowest in patients with diffuse/mixed type tumours (0%) or tumours located in the stomach (4.3%; p < 0.05 for both comparisons). Patients with pCR had 100% probability of overall and disease-free survival (DFS) during the observation period, which was significantly higher (p = 0.037 and p = 0.009, respectively) than the survival probability in patients without pCR. In conclusion, treatment intensification using FLOT was associated with significant pCR rates in patients with oesophagogastric cancer. The distribution of pCR appeared to be significantly different according to histological type and location of the tumours.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Remission Induction; Stomach Neoplasms; Taxoids; Treatment Outcome

Identification and characterization of cancer stem cells (CSCs) in gastric cancer are difficult owing to the lack of specific markers and consensus methods. In this study, we show that cells with the CD90 surface marker in gastric tumors could be enriched under non-adherent, serum-free and sphere-forming conditions. These CD90(+) cells possess a higher ability to initiate tumor in vivo and could re-establish the cellular hierarchy of tumors from single-cell implantation, demonstrating their self-renewal properties. Interestingly, higher proportion of CD90(+) cells correlates with higher in vivo tumorigenicity of gastric primary tumor models. In addition, it was found that ERBB2 was overexpressed in about 25% of the gastric primary tumor models, which correlates with the higher level of CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody) treatment of high-tumorigenic gastric primary tumor models could reduce the CD90(+) population in tumor mass and suppress tumor growth when combined with traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be suppressed when trastuzumab treatment starts at the same time as cell implantation. Therefore, we have identified a CSC population in gastric primary tumors characterized by their CD90 phenotype. The finding that trastuzumab targets the CSC population in gastric tumors suggests that ERBB2 signaling has a role in maintaining CSC populations, thus contributing to carcinogenesis and tumor invasion. In conclusion, the results from this study provide new insights into the gastric tumorigenic process and offer potential implications for the development of anticancer drugs as well as therapeutic treatment of gastric cancers.

Topics: Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Female; Flow Cytometry; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Leucovorin; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Organoplatinum Compounds; Phenotype; Receptor, ErbB-2; Reverse Transcriptase Polymerase Chain Reaction; Spheroids, Cellular; Stomach Neoplasms; Thy-1 Antigens; Trastuzumab; Tumor Burden; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Chemoradiation after surgery for locally advanced gastric cancer improves overall and relapse-free survival compared with observation. However, locoregional recurrences remain high. Accordingly, we instituted this pilot/feasibility study, including intraperitoneal 5-fluoro-2'-deoxyuridine (IP FUDR) as part of the treatment.. Gastric/gastroesophageal junction adenocarcinoma stage Ib-IV (M0) patients who underwent R(0) resection were eligible and had IP catheters inserted at time of surgery. IP FUDR (3 g/dose/day) was given during study days 1-3 and 15-17 before combined 5-fluorouracil, leucovorin, and external beam radiation (45 Gy). Endpoints included toxicity, completion rate, locoregional recurrence, and survival.. Twenty-eight patients (22 men) were enrolled from 2002-2006 at two institutions; their median age was 59.5 years. After R(0) resection, a median 22 (range, 8-102) lymph nodes were examined, and 22 patients had positive nodes. AJCC stages were IB (n = 8), II (n = 10), IIIA (n = 5), IIIB (n = 1), and IV (n = 4). Full-dose IP FUDR and chemoradiation treatment was completed in 20 and 25 patients, respectively. At nearly 4-year median follow-up, 11 patients were disease-free, 5 were alive with disease, 7 were dead of disease, and 1 was dead from other cause; 4 have been lost to follow-up. Recurrences were local in one, intra-abdominal in six, distant in two, multiple sites in two, and unknown in one. The median relapse-free survival is 65.3 months, and the median overall survival has not yet been reached.. IP FUDR before chemoradiation after R(0) gastric cancer resection is well tolerated without compromising completion of postoperative adjuvant treatment. Larger randomized trials studying IP FUDR as part of gastric cancer multidisciplinary treatment are needed to prove efficacy in reducing regional recurrence and improving survival.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Esophagogastric Junction; Feasibility Studies; Female; Floxuridine; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Pilot Projects; Postoperative Period; Prognosis; Radiotherapy Dosage; Stomach Neoplasms; Survival Rate

To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer.. This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol).. Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy.. Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; France; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Postoperative Period; Radiotherapy, Conformal; Retrospective Studies; Risk; Stomach Neoplasms

The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated.. We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted.. In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic.. MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Docetaxel; ErbB Receptors; Female; Fluorouracil; Gene Expression; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Matrix Metalloproteinase 9; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Taxoids; Treatment Outcome; Vascular Endothelial Growth Factor A

To document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer.. A total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12-15 Gy) followed by chemoradiotherapy (EBRT+IOERT group).. The 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p=0.04). Two patients had recurrence within the IOERT field in the EBRT+IOERT group and 14 patients recurred in the same area in the EBRT group (p=0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local-regional control (p=0.02) and disease-free survival (p=0.05). G3/4 late toxicity was observed in 5 patients in the EBRT+IOERT group, but none in the EBRT group (p=0.02).. Higher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chi-Square Distribution; Cisplatin; Docetaxel; Female; Fluorouracil; Gastrectomy; Humans; Intraoperative Care; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Care; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established.. This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences.. There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths.. Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate

To assess efficacy and safety of cetuximab with FOLFOX4 as first-line treatment for advanced gastric cancer.. Cetuximab was administered at 400mg/m2 followed by 250mg/m2 weekly, or 500mg/m2 every 2 weeks. FOLFOX4 regimen was given every 2 weeks (oxaliplatin 85mg/m2, LFA 200mg/m2, 5-FU 400mg/m2 bolus and 600mg/m2 22-hour continuous infusion), for a maximum of 12 cycles, or until the occurrence of untolerated toxicities or disease progression.. Twenty-five patients enrolled from April 2007 to September 2010. With the median treatment of six cycles, patients with complete response, partial response, stable disease and progressive disease were 0, 9, 12 and 4, respectively, according to RECIST criteria. ORR and DCR were 36.0% (95% CI=17%-55%) and 84.0% (95% CI=70%-98%), respectively. The median PFS was 6.5 months (95% CI=5.0-8.0 months) and median OS was 10.6 months (95% CI=4.4-16.7 months). Grade 3-4 toxicities including leucopenia (24%), neutropenia (16%), febrile neutropenia (16%), acne-like rash (16%), sensory neuropathy (8%), diarrhea (4%), nausea and vomiting (4%), asthenia (4%) as well as stomatitis (4%) were observed.. The combination of cetuximab and FOLFOX4 is active and well tolerated as the 1st line treatment for advanced gastric cancer. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. The potential predictive biomarkers for this regimen in treating advanced gastric cancer need to be further identified.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mutation; Organoplatinum Compounds; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Stomach Neoplasms

The aim of this study is to determine the interobserver variability (IV) between radiation oncologists (RO) in target volume delineation for postoperative gastric cancer (GC) radiotherapy planning.. Four physicians were asked to delimitate clinical target volume (CTV) on the same 3D CT images in 9 postoperative radiochemotherapy GC patients. Instructions were given to include tumour bed, remaining stomach, anastomosis, duodenal loop and local lymph nodes. The principal variable was spatial volume discrepancy between the main observer (called "A") and other observers (all called "B"), which were compared using the mathematical formula A⌣B/A⌢B, applied to the 3D CT images using Boolean operators. Analysis of variance with two random effects (observers and patients) was performed.. Mean volumes were 1410 cm(3) for OBA, 1231 cm(3) for OB2, 734.6 cm(3) for OB3 and 1350 cm(3) for OB4. Discrepancies were 519.9±431.6 cm(3) for OB2, 652.1±294.36 cm(3) for OB3 and 225.90±237.07 cm(3) for OB4. Standard deviation ascribed to patients as random effect was 898.6 cm(3) and that ascribed to observers was 198.10 cm(3), considered as a statistically significant difference.. A significant IV in target delineation that can be attributed to many factors depends more on patients' characteristics than RO delineating decisions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Observer Variation; Pilot Projects; Practice Patterns, Physicians'; Prognosis; Prospective Studies; Radiation Oncology; Radiotherapy Planning, Computer-Assisted; Stomach Neoplasms; Tomography, X-Ray Computed

Despite a relatively better prognosis, patients with node-negative gastric cancer still suffer from metastasis and recurrence. To investigae the prognostic factors and appropriate therapies for these pN0 tumors, we analyzed the predictors and evaluated the impact of chemotherapy and extensive lymphadenectomy on survival.. Clinicopathologic features of 153 patients with pN0 gastric cancer were studied retrospectively. The prognostic factors were analyzed stratifying by pT1 and pT2-3 stage. The 5-year survival rate (5-YSR) of patients in different groups of chemotherapy and lymph nodes retrieved were compared.. Multivariate analysis indicated pT, number of nodes retrieved, and chemotherapy as the independent predictors of advanced gastric cancer; anemia was the only independent predictor of early gastric cancer. Survival of patients with pT3 got improved significantly by intraoperative chemotherapy and retrieval of more than 25 nodes, but neither of them benefited patients with pT1-2. Moreover, in pT3 status, 5-YSR of patients with intraoperative chemotherapy was still poorer than those with postoperative chemotherapy and combined chemotherapy.. In pN0 gastric cancers, prognostic factors differed significantly between early stage and advanced stage. For patients with pT3, besides curative gastrectomy and postoperative chemotherapy, it might be beneficial to perform intraoperative chemotherapy and extensive lymphadenectomy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Intraoperative Period; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

The objectives of this study are to investigate the apoptotic changes in gastric adenocarcinoma following neoadjuvant chemotherapy and to illuminate its correlation with response. One 67 gastric cancer patients with cT2-4 or TanyN1-3M0 between January 2006 and December 2007 were included. All patients had previous gastrectomy and D2 lymphadenectomy with curative intent performed. A total of 12 cycles of preoperative mFOLFOX7 chemotherapy was recommended for all patients, and 83 patients received only adjuvant chemotherapy. Resected specimens were subjected to in situ TUNEL assay and scanned with Applied Imaging Ariol SL-50. Apoptosis index (AI) was significantly higher in the patient received preoperative chemotherapy (CS group) than in the patient did not (S group). In the CS group, AI was found to have a strong positive correlation with the pathological response (rho = 0.403, P = 0.0002). A ROC curve presented a score of 49.4 as the AI cutoff value for response, dividing the CS group into two subgroups with significantly different prognoses (P = 0.003) and further allowing identification of 8 patients with significantly better prognosis out of 48 patients evaluated as grades 1a-b according to a pathological response evaluation (P = 0.022). In conclusion, AI is correlated with efficacy of preoperative chemotherapy and prognosis of gastric cancer patients following neoadjuvant chemotherapy. An AI cutoff value for response may be used as a complementary approach to current pathological response evaluations to help identify potential responders.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Female; Fluorouracil; Humans; In Situ Nick-End Labeling; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proportional Hazards Models; Prospective Studies; Stomach Neoplasms; Treatment Outcome

The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer.. The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116.. Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS.. Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Feasibility Studies; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stomach Neoplasms; Time Factors; Treatment Outcome; Turkey; Young Adult

Response to neoadjuvant chemotherapy is an independent prognostic factor in locally advanced gastric cancer. However, no prospectively tested pretherapeutic parameters predicting response and/or survival in gastric cancer are available in clinical routine.. We evaluated the prognostic significance of various clinical pathologic parameters in 410 patients who were treated with neoadjuvant chemotherapy followed by gastrectomy. Clinical and histopathologic response evaluation was performed by using standardized criteria. A prognostic score was created on the basis of the variables identified in the multivariate analysis.. Three pretherapeutic parameters were identified as positive predictive factors for response and prognosis: tumor localization in the middle third of the stomach (P=0.001), well-differentiated tumors (P=0.001), and intestinal tumor type according to Laurén classification (P=0.03). A prognostic index was constructed, dividing the patients into three risk groups: low (n=73), intermediate (n=274), and high (n=63). The three groups had significantly different clinical (P=0.007) and histopathologic response rates (P=0.001) and survival times, with a median survival time that was not reached in the low-risk group, 39.2 months in the intermediate-risk group, and 20.5 months in the high-risk group. The corresponding 5-year survival rates were 65.3, 41.2, and 21.2% (P<0.001), respectively.. A simple scoring system based on three clinicopathologic parameters accurately predicts response and prognosis in neoadjuvant treated gastric cancer. This system provides additional useful information that could be applied to select gastric cancer patients pretherapeutically for different treatment approaches. Prospective testing of the score in an independent patient cohort is warranted.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prognosis; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Rate; Young Adult

We report the case of a 62-year-old woman with a metastatic gastric cancer complicated by diffuse bone marrow carcinomatosis, disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) treated by modified FOLFOX-6 as front-line chemotherapy regimen. This chemotherapy showed clinical, morphological and biological efficiency and safety in this rare and severe hematological complication at initial diagnosis. Furthermore, this is the first case of diffuse bone carcinomatosis from a gastric cancer to be monitored by positron emission tomography integrated computed tomography (PET-CT) scan using 18-fluorodeoxyglucose (18-FDG).

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Carcinoma, Signet Ring Cell; Diagnostic Imaging; Disease Progression; Disseminated Intravascular Coagulation; Drug-Related Side Effects and Adverse Reactions; Fatal Outcome; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Purpura, Thrombotic Thrombocytopenic; Sensitivity and Specificity; Stomach Neoplasms; Treatment Outcome

To investigate the expression pattern and significance of DNA repair genes JWA and X-ray repair cross complement group 1 (XRCC1) in gastric cancer.. Expressions of JWA and XRCC1 were assessed by immunohistochemistry in a training cohort and they went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of JWA and XRCC1 expression status in cases treated with surgery alone or combined with adjuvant chemotherapy was evaluated, respectively.. JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent noncancerous tissues. Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expressions, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01). However, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI: 0.26-0.73; P = 0.002, and HR = 0.44, 95% CI: 0.26-0.75; P = 0.002, respectively); Adjuvant fluorouracil-leucovorin-platinol (FLP) did not improve OS, except in the patients with low JWA and XRCC1 expressions (P = 0.010 for JWA and 0.024 for XRCC1, respectively).. JWA and XRCC1 protein expressions in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant platinum-based chemotherapy (FLO or FLP) in resectable human gastric carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; China; Cohort Studies; DNA-Binding Proteins; Down-Regulation; Female; Fluorouracil; Heat-Shock Proteins; Humans; Intracellular Signaling Peptides and Proteins; Leucovorin; Male; Membrane Transport Proteins; Organoplatinum Compounds; Oxaliplatin; Prognosis; Stomach Neoplasms; Treatment Outcome; X-ray Repair Cross Complementing Protein 1

We aimed to clarify the prognostic significance of HER2 positivity in advanced gastric cancer.. The cohort included patients with initially metastatic or recurrent gastric cancer treated with first-line modified FOLFOX-6. The HER2 status was analyzed according to modified scoring criteria specific for gastric cancer.. HER2 positivity was shown in 10 out of 114 patients (9.0%). The median time-to-progression (TTP) (4.3 months, 95% confidence interval (CI)=3.6-4.9) and the overall survival (OS) (7.5 months, 95% CI=6.1-8.8) of patients with HER2-positive gastric cancer tended to be shorter than the median TTP (5.9 months, 95% CI=4.5-7.2) and OS (10.8 months, 95% CI=9.2-12.3) of those with HER2-negative gastric cancer (TTP, p=0.177; OS, p=0.068). Particularly in the subgroup of patients without diffuse-type histology, HER2-positive gastric cancer had a worse TTP than those with HER2-negative gastric cancer (p=0.024). In multivariate analysis of this subgroup, HER2 positivity and ECOG performance status of 2 were associated with shorter TTP (hazard ratio (HR)=2.926, p=0.014; HR=2.489, p=0.035, respectively).. HER2-positive gastric cancer seems to confer poorer prognosis, particularly in patients without diffuse-type tumor, treated with modified FOLFOX-6.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Female; Fluorouracil; Genes, erbB-2; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Prognosis; Recurrence; Stomach Neoplasms; Treatment Outcome

Since 2007, S-1 plus cisplatin therapy has been recognized as the standard first-line treatment for advanced gastric cancer in Japan. However, no standard regimen has been established for patients refractory to first-line treatment. Furthermore, irinotecan and paclitaxel are considered key drugs for second-line treatment. Several studies have investigated the efficacy and tolerability of combination therapy with oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-6) for advanced gastric cancer. Here, we examined the efficacy and toxicity of modified FOLFOX-6 therapy in heavily pretreated patients with advanced gastric cancer refractory to 5-fluorouracil, irinotecan, cisplatin and taxanes.. Fourteen patients with advanced gastric cancer refractory to 5-fluorouracil, irinotecan, cisplatin and taxanes were included in the study. In modified FOLFOX-6 therapy, 85 mg/m(2) oxaliplatin, 400 mg/m(2) 5-fluorouracil and 200 mg/m(2) leucovorin on Day 1 were administered biweekly by intravenous infusion, followed by the administration of 2400 mg/m(2) 5-fluorouracil by a 46-h continuous infusion.. The median age of the patients was 59 years (range, 22-74). A median of 5.5 (range, 1-13) chemotherapy cycles were administered. The overall response rate was 23.1% in patients with measurable lesions. Of the 12 patients with advanced gastric cancer refractory to cisplatin, 2 showed partial response (response rate, 18.2%). The progression-free survival was 90 days, and the median survival time from the initiation of modified FOLFOX-6 therapy was 268 days. Grade 3-4 toxicities most commonly observed included neutropenia (57%), anaemia (14%), thrombocytopenia (21%) and hyperammonaemia (7%).. Modified FOLFOX-6 therapy in patients refractory to 5-fluorouracil, irinotecan, cisplatin and taxanes may be a potential advanced gastric cancer therapeutic strategy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Retreatment; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Taxoids; Young Adult

The patient was a 72-year-old woman, admitted to our hospital due to appetite loss. We performed gastroscopy, colonoscopy and abdominal CT. She had both advanced ascending colon cancer with multiple liver metastasis(cStage IV: cT3N1H3)and early gastric cancer(cStage 0: cTisN0M0). She received chemotherapy with modified FOLFOX6(mFOLFOX6), and the chemotherapy was judged effective for her gastric cancer. During the next 6 months, a total of 10 courses had been performed. The tumor marker scores(CEA, CA19-9)decreased significantly. Gastric cancer was diagnosed as CR(complete response)in gastroscopy after 6 courses of chemotherapy. In this case, chemotherapy with mFOLFOX6 was effective for gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Neoplasms, Second Primary; Organoplatinum Compounds; Stomach Neoplasms; Tomography, X-Ray Computed

The administration of the de Gramont regimen in combination with cisplatin and epirubicin (modified ECF) has previously been reported as a treatment for advanced gastric cancer, but here we report this regimen combination in an adjuvant setting for the first time.. Forty-eight patients with curatively resected gastric cancer were treated. Each 2-week cycle consisted of epirubicin (50 mg/m(2)), cisplatin (50 mg/m(2)), 5-fluorouracil (5-FU) IV bolus (400 mg/m(2)) and 5-FU IV (2,400 mg/m(2)) over 46 h plus leucovorin IV (400 mg/m(2)) over 2 h. Postoperative chemoradiotherapy was also administered to the patients when indicated. We retrospectively reviewed the patients who were treated with modified ECF.. The median disease-free survival (DFS) was 40.7 months and the 1-, 3- and 5-year DFS rates were 78.5, 55.7 and 44.6%, respectively. The most common grade 3-4 toxicities were hematological and gastrointestinal.. A modified ECF regimen may be an effective and convenient treatment with tolerable toxicities for the adjuvant treatment of gastric cancer. It may provide an alternative regimen to the standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Recurrence; Retrospective Studies; Stomach Neoplasms; Survival Rate

Gastric cancer is one of the most common types of malignant tumors in China and East Asia and has the highest mortality rate of the malignant gastrointestinal tumors. Neoadjuvant chemotherapy is a systemic or local chemotherapy that is given prior to the local treatment of malignant tumors. Neoadjuvant therapy is currently showing some positive prospects; however, its clinical effects remain controversial. In this study, we used the modified FOLFOX7 (mFOLFOX7) regimen as a neoadjuvant chemotherapy regimen. Perioperative clinical and pathological efficacy, toxicity, effects of surgery, postoperative observation, and prognosis were studied to investigate its clinical efficacy and safety.. Eighty patients with advanced gastric cancer were treated in our surgery department from 2005 to 2009; 38 of these patients received mFOLFOX7 neoadjuvant chemotherapy, the other 42 patients assigned to the control group. The perioperative effects of mFOLFOX7 chemotherapy, including clinical effects and toxicity, were observed in each patient.. After mFOLFOX7 chemotherapy, clinical and pathologic stages decreased in 21.1% and 36.8% of the patients, respectively, but the results were not statistically significant (P = 0.129). The clinical response rate was 50% (19/38). Toxicity was mild; most adverse events were grade I or II and involved no severe infections or deaths. Compared with the control group, the radical resection rate increased (92.1% vs. 85.7%; P = 0.437); surgical effects were completed without an increased incidence of perioperative complications. The 1-, 2-, and 3-year survival rates were 78.70%, 57.40%, and 51.66%, respectively, in the neoadjuvant chemotherapy group and 78.57%, 56.87%, and 43.16%, respectively, in the control group.. The mFOLFOX7 regimen was very effective and well-tolerated as a neoadjuvant chemotherapy for advanced gastric cancer. However, the 1-, 2-, and 3-year survival rates in the mFOLFOX7 group were not significantly different from the control group.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Stomach Neoplasms

In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48 h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7 ± 111.5 U/l [pre mean] vs. 983.3 ± 214.1 U/l [post mean], p = 0.01; M65, 2,061.7 ± 431.2 U/l [pre mean] vs. 2,646.3 ± 433.1 U/l [post mean], p = 0.003). Means of the differences of M30 and M65 levels before and 48 h after chemotherapy were 400.5 ± 190 U/l ([M30-difference] M30-D) and 584.6 ± 335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3 months, p = 0.018 and OS, 13.6 vs. 8.1 months, p = 0.029). In addition, median PFS and OS intervals in patients with serum M65-D > 584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4 months for PFS, p = 0.002 and 5.7 vs. 13.6 months for OS, p = 0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (p = 0.02 and p = 0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (p = 0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48 h after chemotherapy and these were poor pr

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Signet Ring Cell; Cisplatin; Docetaxel; Enzyme-Linked Immunosorbent Assay; Female; Fluorouracil; Follow-Up Studies; Humans; Keratin-18; Leucovorin; Male; Middle Aged; Neoplasm Staging; Peptide Fragments; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids

The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer.. A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, http://epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared.. In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P < 0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups.. For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Routes; Epirubicin; Etoposide; Female; Fluorouracil; Follow-Up Studies; Humans; Injections, Intra-Arterial; Injections, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis; Stomach Neoplasms; Survival Rate

Trastuzumab in combination with doublet chemotherapy (cisplatin and fluoropyrimidine) is a standard treatment for patients with HER2-positive advanced gastric cancer. There have been no studies evaluating trastuzumab with more intensive triplet chemotherapy regimens in this setting. We report the treatment outcome in 3 patients with HER2-positive metastatic gastric cancer who were treated with trastuzumab plus the triplet FLOT regimen (5-fluorouracil/leucovorin, oxaliplatin, and docetaxel).. 3 patients with HER2-positive metastatic gastric cancer received trastuzumab plus FLOT. Trastuzumab 4 mg/kg was given with the 2nd chemotherapy cycle and was continued at 2 mg/kg every week with subsequent cycles.. All 3 patients had a dismal prognosis because of their heavy disease burden, most notably extensive hepatic metastatic involvement. Patients tolerated the triple-drug plus trastuzumab combination well. All patients exhibited a dramatic clinical response.. This report provides the first evidence that the addition of trastuzumab to a docetaxel-based, triple-drug chemotherapy combination is feasible and highly active in patients with HER2-positive metastatic gastric cancer.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Receptor, ErbB-2; Stomach Neoplasms; Taxoids; Trastuzumab; Treatment Outcome

There is no established standard salvage chemotherapy in the second-line setting for patients with advanced gastric cancer (AGC) pre-treated with platinum and taxane-based chemotherapy. Our study aims to evaluate the safety and efficacy of FOLFIRI regimen (irinotecan with leucovorin and bolus and continuous infusion with 5-fluorouracil) as a salvage chemotherapy regimen in patients with AGC. Medical records of 97 patients with AGC who received second-line FOLFIRI regimen between March 2006 and February 2011 were examined. Complete and partial responses were observed in 3 (3.1%) and 23 (23.7%) patients, respectively. The median time to progression (TTP) was 3.5 months (95% CI: 2.4-4.6) and the median overall survival (OS) was 10.5 months (95% CI: 8.8-12.2). The most common observed grade 3/4 toxicities were neutropenia (23.7%), diarrhea (6.2%), and stomatitis (5.2%). FOLFIRI regimen is safe and effective in the second-line treatment of AGC patients pre-treated with cisplatin and taxanes.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Resistance, Neoplasm; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neutropenia; Platinum Compounds; Remission Induction; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Survival Analysis; Taxoids; Young Adult

A 71 years old Italian man had type 3 gastric cancer of the greater curvature. Total gastrectomy with splenectomy and D2 lymph node dissection were performed. After discharge chemotherapy ELF regimen was administered for 6 months. After 16 months from the operation a local recurrence was discovered by CT scan. Surgical en-bloc resection was performed removing pancreatic tail, splenic colic flexure and a portion of left diaphragm. Histological examination confirmed local recurrence of gastric adenocarcinoma infiltrating pancreas, colon and diaphragm with lymph node metastasis.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Etoposide; Fluorouracil; Gastrectomy; Humans; Levoleucovorin; Male; Neoplasm Recurrence, Local; Stomach Neoplasms; Tomography, X-Ray Computed

Dismal clinical results in patients with unresectable advanced or recurrent gastric cancer highlight the need for effective systemic chemotherapy. An increase in adverse events associated with systemic chemotherapy is shown in elderly patients, but it remains controversial whether they should receive the same chemotherapy used for younger patients. We retrospectively studied 73 patients with unresectable advanced or recurrent gastric cancer, including 48 nonelderly patients (<65 years old) and 25 elderly patients (≥65 years old) who received a combination of oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-4, mFOLFOX-4 regimen).. From January 2006 to June 2011, 73 patients with histologically confirmed unresectable advanced or recurrent gastric cancer were enrolled in this study. All patients were treated with an mFOLFOX-4 regimen of 85 mg/m(2) of oxaliplatin and 200 mg/m(2) of leucovorin on the first day, followed by a 24-hour continuous infusion of 1,000 mg/m(2) of 5-fluorouracil in 2 days with a 2-week interval. Treatment continued until disease progression or intolerable adverse events occurred.. Overall response rates show clinical efficacy (41.1%, 30/73 patients), stable cancer (26.0%, 19/73 patients) and progressive cancer (32.9%, 24/73 patients). The response rate was 36.0% in the elderly group and 43.8% in the nonelderly group (p = 0.891). In elderly patients, the overall time to progression was 8.1 months and the median overall survival was 11.9 months. On the other hand, in nonelderly patients, the overall time to progression was 7.9 months (p = 0.483) and the median overall survival was 11.2 months (p = 0.953). The results show no statistical differences in efficacy and adverse events between elderly and nonelderly groups (all p > 0.05).. The mFOLFOX-4 therapy is an effective and safe first-line treatment for unresectable advanced or recurrent gastric cancer patients. Moreover, mFOLFOX-4 was well tolerated and effective in both nonelderly and elderly patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Recurrence; Retrospective Studies; Stomach Neoplasms; Survival Rate

The efficacy of adjuvant chemotherapy for advance resectable gastric cancer is controversial. Recently, less than 20% of the patients that received surgery can survive locally advance gastric cancer for 5 years. The purpose of the present study was to compare the therapeutic efficacy of the combination 5-fluoruracil (5-FU) with cisplatinum based and single 5-FU based regimen for the treatment of gastric cancer after post-operative gastric resection.. Patients were recruited if they underwent curative RO gastric resection surgery with standard Dl or D2 lymph node dissection. Between 2002 and 2007, we conducted a cohort study, and collected prospective data of 88 patients with advanced gastric cancer They were analyzed for median survival time and rate, recurrence rate, and chemotherapy toxicity prevalence. The median survival time was the primary study endpoint. The median survival time was compared between groups by a log-rank test.. In the present study, combined 5-FU based regimen did not show a significantly superior survival time to single 5-FU regimen, both poor stage groups had better median survival in both combined 5-FU and single 5-FU regimen when compared to surgery. There was more than 50 months median survival in the first group, and 52 months in the latter However, in cisplatinum with 5-FU group, there are only a small number of signet ring cells. In addition, those have poorer clinical profile before treatment (p = 0.003). No difference on mortality rate related to toxicity.. Both regimens are useful regimens with efficient benefit for gastric cancer patients as well as a cheaper regimen than other new combination drug regimens. However second line drug or other combined second generation based chemotherapy regimen that has similar action to cisplatinum such as oxaliplatin may be safer for toxicity, and may get better out outcome. 5-FU regimen is still the reference group in future clinical trial for advanced gastric cancer treatment. The value of any new adjuvant treatment approach could be proven by a randomized study comparing it with cisplatinum based regimen plus 5-FU or single 5-FU regimen.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Invasiveness; Prospective Studies; Stomach Neoplasms

Platinum and 5-fluorouracil (5-FU)-based regimens have been used the most frequently in palliative chemotherapy for gastric cancer. The present study evaluated the prognostic significance of Bax, excision repair cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) in advanced gastric cancer patients treated with 5-FU, leucovorin, and oxaliplatin (FOLFOX) palliative chemotherapy.. Seventy-two patients with metastatic or recurrent gastric cancer were treated with FOLFOX regimen. Pretreatment tumor biopsy specimens were analyzed for Bax, ERCC1, and TS expression by immunohistochemistry.. High expression of Bax, ERCC1, and TS was observed in 31 (43%), 33 (46%), and 35 (49%) patients, respectively. The median overall survival (OS) of patients was 12 months. Low expression of Bax was associated with poor OS (median, 9 months vs. 18 months; 2-year, 10% vs. 48%; p=0.0005) in univariate analysis, while expression of ERCC1 and TS was not correlated with patient outcome. In multivariate analysis, low expression of Bax was a significant independent predictor of poor OS (p=0.028). Low expression of Bax was significantly associated with poor survival of patients with metastatic or recurrent gastric cancer treated with FOLFOX chemotherapy.. Immunohistochemical staining for Bax with pretreatment biopsy specimen may be useful in selecting FOLFOX regimen as a treatment option for advanced gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; bcl-2-Associated X Protein; Biomarkers, Tumor; Biopsy; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Gastric Mucosa; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Predictive Value of Tests; Prognosis; Retrospective Studies; Stomach; Stomach Neoplasms; Thymidylate Synthase; Treatment Outcome

Gastric cancer is the third most common cancer worldwide and the second leading cause of cancer deaths. Appropriate staging and treatment options relate to the stage of disease and performance status of the patient.. Here we present the case of a 72 year old male, with an initial presentation of apparently locally advanced gastric cancer. On discovery of metastatic disease, the utility of palliative gastrectomy, and first and second line chemotherapy are discussed.. This case demonstrates the potential value of sequential lines of chemotherapy in good performance status patients with advanced gastric cancer. Further research will be necessary in order to assess the utility of newer targeted agents in this setting.

Topics: Adenocarcinoma; Adenoma, Villous; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Fluorouracil; Gastrectomy; Humans; Leucovorin; Liver Neoplasms; Male; Neoplasm Staging; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Treatment Outcome

A 71-year-old man receiving maintenance dialysis because of diabetic nephropathy presented with hematemesis at another hospital in January 2008. A gastrointestinal endoscopy demonstrated a II a-like lesion in the angle of the stomach, and he was admitted to our hospital. A diagnosis of gastric adenocarcinoma (cT2N2M0, Stage IIIA) was made. An operation could not be performed because of the high risk, so combination chemotherapy with 5-FU and l-LV was initiated. After 3 courses of treatment, the size of the primary tumor was markedly reduced. After 6 courses, the primary lesion had changed to a scar, and an endoscopic biopsy revealed no cancer cells. His performance status did not deteriorate, and no serious adverse events occurred during the course of treatment. Chemotherapy was continued because the overall response was SD. 5-FU/l-LV therapy should be considered as a safe and useful treatment for a hemodialysis patient with advanced gastric cancer.

Topics: Aged; Biopsy; Fluorouracil; Humans; Kidney Failure, Chronic; Leucovorin; Male; Neoplasm Staging; Renal Dialysis; Stomach Neoplasms

The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV).. From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57).. Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months.. Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Palliative Care; Prognosis; Radionuclide Imaging; Stomach Neoplasms; Treatment Outcome

Metabolic imaging of gastric cancer is limited due to the 30% of primary tumors that are not (18)F-fluorodeoxyglucose (FDG) avid. In contrast, the proliferation marker (18)F-fluorothymidine (FLT) has been shown to visualize also non-FDG-avid gastric tumors. In this study we tested whether FLT-positron emission tomography (PET) can improve the predictive potential of molecular imaging for assessing response to neoadjuvant therapy in gastric cancer compared with FDG-PET.. 45 patients with gastric cancer underwent FDG- and FLT-PET before and 2 weeks after initiation of chemotherapy. FDG/FLT-PET findings and Ki67 immunohistochemistry were correlated with clinical and histopathological response and survival.. 14 patients had non-FDG-avid tumors, whereas all tumors could be visualized by FLT-PET. No significant association of clinical or histopathological response with any of the analyzed metabolic parameters [initial standardized uptake value (SUV), SUV after 2 weeks, change of SUV for FDG/FLT] was found. Univariate Cox regression analysis for Ki67 and metabolic parameters revealed significant prognostic impact for survival only for FLT SUV(mean) day 14 (p=0.048) and Ki67 (p=0.006). Multivariate Cox regression analysis (including clinical response, Lauren type, ypN category, and FLT SUV(mean) day 14) revealed Lauren type and FLT SUV(mean) day 14 as the only significant prognostic factors (p=0.006, p=0.002).. FLT uptake 2 weeks after initiation of therapy was shown to be the only imaging parameter with significant prognostic impact. Neither FLT-PET nor FDG-PET were correlated with histopathological or clinical response. However, these data must be interpreted with caution due to the single-center trial study design, relatively short follow-up, poor response rates, and unfavorable prognosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cisplatin; Dideoxynucleosides; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Glucose; Humans; Immunoenzyme Techniques; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Stomach Neoplasms; Survival Rate

Prognosis of metastatic gastric cancer is poor and median survival is between 3 and 5 months. Response rates of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in first-line treatment have been found to be 20-25% in the English literature. It has been demonstrated that adding docetaxel to combination chemotherapy improved time to progression and overall survival. However, the toxicity rates of the docetaxel-cisplatin-5-FU protocol were high. In our study we compared efficacy and toxicity of cisplatin-5-FU-folinic acid (CFF) and modified docetaxel-cisplatin-5-FU (mDCF) regimens in the first-line treatment of metastatic gastric cancer.. Between June 2004 and October 2008, 70 patients with previously untreated metastatic gastric cancer treated with CFF (n = 30) and mDCF (n = 40) were retrospectively evaluated in the study. Survival and toxicity data were compared.. Median age of the patients was 53 years (range 23-69). Forty-eight percent of the patients were male and 75.7% had an ECOG performance status of 0-1. Prognostic factors including age, ECOG performance status, histopathological grade, and number and sites of metastases were similar between the groups. Objective response rates (complete and partial response) were higher in the mDCF group (30.0 vs. 13.3%, p = 0.19). While toxicity was acceptable in both groups, the most common grade 3-4 toxicities were anemia in 3.3 and 5.0%, neutropenia in 20 and 7.5%, febrile neutropenia in 6.7 and 5.0%, and diarrhea in 3.3 and 5.0% in the CFF and mDCF groups, respectively. Median follow-up was 10.3 (1.5-59.6) months. During that period 90 and 97.5% of the patients were dead in the CFF and mDCF groups, respectively. Median time to progression was 4.4 (95% CI 1.8-7.0) and 6.2 months (95% CI 5.6-6.8) (p = 0.85), median overall survival was 6.5 (95% CI 1.8-11.2) and 8.7 months (95% CI 6.7-10.7) (p = 0.88) in the CFF and mDCF groups, respectively.. The mDCF regimen has been found to be more favorable than the CFF regimen with an acceptable toxicity profile in the first-line treatment of metastatic gastric cancer.

Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids

Management of gastric cancer in older adults is challenging. Perioperative treatment with epirubicin, cisplatin, and 5-fluorouracil combination chemotherapy and surgery is considered the standard treatment of locally advanced gastric adenocarcinoma. However, this chemotherapy regimen is not well tolerated in older adults. Here, we report a case of an older patient with locally advanced gastric cancer who was treated with modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) regimen and achieved a complete pathological response.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Treatment Outcome

This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy.. We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy.. There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups.. The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Postoperative Complications; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Postoperative chemoradiation as per Intergroup-0116 trial ("Macdonald regimen") is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0).. Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test.. Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts.. In our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic, with a mortality rate which seems higher than reported in that trial. Efficacy data appears comparable to the original report. Following postoperative chemoradiation, involvement of surgical margins still has a detrimental impact on patient outcome.

Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Postoperative Period; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

For patients with HER2-overexpressing gastric cancer, there is an improved prognosis with additional trastuzumab to chemotherapy with a platinum compound and a fluoropyrimidin in first-line therapy. Second-line combinations are currently evaluated in various studies.. We report the case of a 43-year-old male patient who came to our hospital with recurrent metastatic gastric cancer after curative surgery 18 months before. His disease responded well to several therapeutic regimens. Firstline chemotherapy with a combination of epirubicin, oxaliplatin and capecitabine (EOX) and the following therapies -- peritonectomy, multivisceral resection, hyperthermic intraperitoneal chemotherapy (HIPEC), and secondline chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (FLO) - induced a complete remission. At the time of the subsequent progression, HER2 overexpression was detected. We administered the combination of irinotecan, 5-fluorouracil, leucovorin (FOLFIRI) and trastuzumab, which to our knowledge was used for the first time in a patient with metastatic gastric cancer in third-line therapy. This regimen again induced a complete remission of the disease, which has been sustained now for at least 8 months.. This is the first time in the literature that a combination of FOLFIRI and trastuzumab (FOLFIRIT) was used successfully in a patient with recurrent metastatic gastric cancer.

Topics: Abdominal Neoplasms; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Fluorouracil; Gastrectomy; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Receptor, ErbB-2; Reoperation; Stomach Neoplasms; Tomography, X-Ray Computed; Trastuzumab; Ultrasonography

We retrospectively analyzed comparative toxicities and efficacies of chemotherapy regimens in advanced gastric cancer (AGC) patients who achieved complete response (CR) after chemotherapy.. We reviewed the medical records of 1,203 patients, who were pathologically diagnosed as AGC in a single center between January 2001 and October 2007. On the basis of the Response Evaluation Criteria in Solid Tumors, CR was evaluated with abdominal computed tomography. Toxicities were evaluated using the National Cancer Institute's common toxicity criteria before each chemotherapy cycle.. Among the 1,203 AGC patients enrolled in this study, 568 received chemotherapy and 635 received best supportive care. The major chemotherapy regimens were 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), docetaxel, cisplatin and 5-fluorouracil (DCF) and 5-fluorouracil, leucovorin and irinotecan (FOLFIRI). Among the 568 patients, 51 (9.0%) achieved CR (49 [8.6%] with FOLFOX [n=12], DCF [n=26], or FOLFIRI [n=11] and 2 [0.3%] with etoposide, leucovorin and 5-fluorouracil). For patients administered FOLFOX, DCF, and FOLFIRI, the median time to disease progression was 4 months (range, 1.8-59.5), 15 months (range, 2.9-31.2) and 10 months (range, 2.0-39.5), and the median survival times were 48 months (range, 5.9-74.0), 37 months (range, 14.0-86.0), and 30 months (range, 6.0-50.0), respectively. Grades 3-4 mucositis occurred mostly in patients administered DCF (n=8, 30.8%). Grades 3-4 leucopenia were observed in 1 (8.3%), 11 (42.3%), and 4 (36.4%) patients administered FOLFOX, DCF and FOLFIRI, respectively. No statistically significant differences were observed in the 3 regimens.. All 3 regimens (FOLFOX, DCF and FOLFIRI) were active and tolerable. Their efficacies and toxicities were not significantly different.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Mucositis; Nausea; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tomography, X-Ray Computed; Vomiting

This is a very rare case report of multiple small intestine cancer in jejunal loop of Roux-en-Y re-construction, duodenum and jejunum. A 51-year-old man had undergone total gastrectomy by Roux-en-Y re-construction for Stage III B gastric cancer in 1997. In 2008, he underwent partial jejunectomy and partial ilectomy for ileus due to small intestine adenocarcinoma, located at the jejunum 50 cm distal from Roux-en-Y anastomotic region and at the ileum 20 cm proximal from the ileocecal region. PET/CT suspected a recurrence and peritoneal dissemination, so he had undergone S-1/docetaxel treatment since 2009. In 2010, he was diagnosed as obstructive jaundice due to duodenal tumor revealed by CT. Furthermore, enteroscopy revealed duodenal advanced cancer, type 2 advanced cancer and five polyps in jejunal loop, type 2 advanced cancer and type II a early cancer in jejunum. He could not undergo both pancreatoduodenectomy and choledochojejunostomy because of the invasion to hepatoduodenal ligament. He underwent partial jejunectomy for the advanced cancer in jejunal loop 10 cm proximal form Roux-en-Y anastomotic region and in jejunum 50 cm distal from Roux-en-Y anastomotic region for prevention of ileus.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Gastrectomy; Humans; Jejunal Neoplasms; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Organoplatinum Compounds; Stomach Neoplasms

This retrospective study investigated the impact of neoadjuvant chemotherapy on the number of lymph nodes harvested in patients with T(3)/T(4) gastric cancer. Lymph node counts in 58 patients who received preoperative neoadjuvant chemotherapy were compared with those in 168 patients who received surgery alone. Significantly more patients (n = 14, 24.1%) treated with neoadjuvant chemotherapy had < 15 lymph nodes harvested compared with patients (n = 13, 7.7%) treated with surgery alone. A significant correlation between the total number of harvested lymph nodes and the number of metastatic lymph nodes (mLNs) existed in both groups. Neoadjuvant chemotherapy was the only factor associated with the retrieval of < 15 lymph nodes. The number of mLNs was an independent predictive factor for overall survival. Although neoadjuvant chemotherapy decreased the number of lymph nodes harvested, the number of mLNs may still be an acceptable prognostic factor in patients with gastric cancer, following neoadjuvant chemotherapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Demography; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Proportional Hazards Models; Stomach Neoplasms

Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60 mg/m(2) docetaxel and cisplatin for 1 day and 600 mg/m(2)/day, 5-flourouracil infusion for 5 days, repeated every 3 weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23-65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1 months. The longest follow-up time was 19.9 months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7 months and overall survival was 10 months. The assessment of patients for grade 3-4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Docetaxel; Dose-Response Relationship, Drug; Female; Fever; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neutropenia; Retrospective Studies; Stomach Neoplasms; Taxoids; Young Adult

The aim of this study was to evaluate the efficacy and toxicity of docetaxel (TAX), cisplatin (CDDP), and fluorouracil (5-FU) plus leucovorin (CF) as the neoadjuvant chemotherapy (NACT) regimens in the treatment of nonresectable advanced gastric cancer. Twelve patients with nonresectable advanced gastric cancer were treated with NACT regimens consisted of docetaxel, cisplatin, fluorouracil, plus leucovorin before operation. Nine of the 12 patients were downstaged and 8 were radically operated after the end of the NACT. The overall response rate was 75% with 8.3% complete response and 66.7% partial response, and the ascites disappeared in 63.6%. The most common toxicities were bone marrow suppression, nausea, vomiting, alopecia, and heptoses. The toxicities were recoverable after symptomatic treatment. The results confirmed that the combination of docetaxel, cisplatin, fluorouracil plus leucovorin (CF) is a very effective and well-tolerated regimen as NACT for the patients with nonresectable advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Remission Induction; Stomach Neoplasms; Survival Rate; Taxoids; Tomography, X-Ray Computed; Treatment Outcome

We performed retrospective study in order to compare oxaliplatin, leucovorin, and fluorouracil (FOLFOX) versus irinotecan, leucovorin, and fluorouracil (FOLFIRI) in recurred or metastatic gastric adenocarcinoma.. We investigated 56 patients who were diagnosed with recurred or metastatic gastric adenocarcinoma in a single center during march, 2003 to march, 2008. The patients received either FOLFOX or FOLFIRI chemotherapy.. There were no significant difference between the Oxaliplatin group (30 patients) and Irinotecan group (26 patients) in sex, age, and ECOG performance (p<0.05). Oxaliplatin group showed 1 case of CR (3.3%) and 12 cases of PR (40%), making the response rate 43.3%. Irinotecan group showed CR in 2 cases (7.7%) and PR in 10 cases (38.5%), making the response rate 46.2%. The median value of time to progression was 4 months in the oxlaplatin group and 4.5 months in the irinotecan group. The overall survival showed no significant difference (p=0.784), with the irinotecan group (9.7 months) being slightly longer than the Oxaliplatin group (8.3 months). Grade 3/4 neutropenia occurred similarly in both groups (4 cases in the oxalplatin group, 9 in the irinotecan group).. Both combination treatment can be used safely and effectively in recurred or metastatic gastric adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Recurrence; Retrospective Studies; Stomach Neoplasms; Survival Analysis

Gastric cancer is one of the most common malignancies in the world. The routes of metastasis include direct extension, lymphatics, and peritoneal or hematogenous spread. Testicular metastasis is rare. We present here a 23-year-old gastric cancer patient who first presented with right-side testis swelling and pain. Diagnosis of metastatic adenocarcinoma was made after right-side orchiectomy. Gastric adenocarcinoma with ascites and peritoneal seeding was found after esophagogastroscopy and abdominal computed tomography. The patient received chemotherapy consisting of docetaxel 36 mg/m(2) and cisplatin 30 mg/m(2) on day 1 and day 8, plus oral tegafur/uracil 300 mg/m(2)/day and leucovorin 90 mg/day on day 1 to day 14 in a 21-day cycle, and he had a partial response to the chemotherapy. Metastatic tumors, especially gastric adenocarcinoma, should be considered in the differential diagnosis of patients presenting with testicular mass and they may respond well to chemotherapy.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Humans; Leucovorin; Male; Stomach Neoplasms; Taxoids; Tegafur; Testicular Neoplasms; Uracil

This report presents a rare patient with cardiac tamponade as the first manifestation of primary gastric signet-ring cell carcinoma.. A 56-year-old woman with emergent dyspnea, anterior chest oppression, and hypotension was diagnosed as having cardiac tamponade due to massive pericardial effusion. The endoscopic examination of the stomach disclosed gastric cancer in the posterior wall of the antrum and the biopsy showed signet-ring cell carcinoma. The gastric cancer was complicated by malignant pericardial effusion and pleural effusion as well as metastasis to the peripheral lymph nodes and bones. The patient was treated with percutaneous pericardiocentesis followed by systemic chemotherapy (oxaliplatin and sequential 5-fluorouracil plus leucovorin). The pericardial effusion gradually disappeared and there was no cardiac tamponade occurrence. The patient has survived more than 6 months so far.. Cardiac tamponade may originate from a primary gastric signet-ring cell carcinoma. Pericardiocentesis followed by systemic chemotherapy may be effective in controlling such advanced gastric signet-ring cell carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cardiac Tamponade; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Radiography; Stomach Neoplasms; Treatment Outcome

The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy.. Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns.. With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P = .0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P = .001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival.. After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Netherlands; Proportional Hazards Models; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Stomach Neoplasms; Time Factors; Treatment Outcome

To explore if vascular endothelial growth factor receptor-3 (VEGFR-3) and carcinoembryonic antigen (CEA) can predict overall survival in advanced gastric cancer.. VEGFR-3 level was assessed by enzyme-linked immunosorbent assay, and CEA was assessed by chemiluminescence immunoassay in the sera of 81 advanced gastric cancer patients before treatment with oxaliplatin plus 5-fluorouracil and folinic acid.. Median survival time in patients with a low serum VEGFR-3 level was significantly longer than in those with a higher VEGFR-3 level (15.4 mo vs 7.7 mo, P < 0.001). Patients with a low CEA level had a longer survival than those with a higher CEA level (15.8 mo vs 8.6 mo, P < 0.001). Thirty-nine patients with low VEGFR-3 and low CEA levels had a median survival of 19.7 mo (P = 0.0006). The hazard ratio for patients with a high VEGFR-3 level was 2.443 (P = 0.002).. High serum VEGFR-3 level is correlated significantly with poor survival. In patients with a high serum level of VEGFR-3, alternative chemotherapy regimens should be considered.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Case-Control Studies; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Stomach Neoplasms; Vascular Endothelial Growth Factor Receptor-3

Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs.. From 1994 to 2000, data from a total of 61 patients with resectable gastric cancer were analyzed. Peritoneal cytology was performed before NAC at laparoscopy and at tumor resection. A minimum of 6 weeks of NAC, consisting of cisplatin, folinic acid, and fluorouracil, was administered. FPTCs were detected immunohistochemically with Ber-EP4 antibody.. No FPTCs could be detected in 42 patients (69%), compared to 19 (31%) with FPTCs before NAC. During chemotherapy, 10 (24%) of 42 patients developed FPTCs, and 7 (37%) of 19 patients reverted from positive to negative. Patients who became FPTC negative (n = 7) showed an improved median survival (36.1 months) and a longer 2-year survival (71.4%) compared to FPTC-positive patients before and after NAC (n = 12), with a median survival of 9.2 months and a 2-year survival rate of 25%. In contrast, patients who reverted from FPTC negative to positive during NAC (n = 10) had a median survival of 18.5 months and a 2-year survival of only 20%. Multivariate analysis identified ypN category and FPTC change as independent prognostic factors.. NAC for patients with positive cytology could lead to FPTC negativity in a subset of patients and improve their prognosis. However, NAC might be a risky strategy for almost one-quarter of patients whose disease develops positive cytology.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Neoplasms; Laparoscopy; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplastic Cells, Circulating; Peritoneal Cavity; Peritoneal Lavage; Peritoneal Neoplasms; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity.. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients.. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus.. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to hematological toxicity, mainly febrile neutropenia. This should prompt us to review the subsequent chemotherapy protocol and make it more tolerable.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

The case is a 66-year-old woman. CT showed multiple metastasis of the liver and lung after operation by colectomy for ascending colon carcinoma. A close inspection showed progressive stomach cancer with lymph node metastasis. Metastasis was considered an effect when it was of colon cancer origin, and treatment by mFOLFOX6 was started. In the results, we confirmed contraction of the liver and lung metastasis and contraction of the regional lymph node metastasis of the stomach by CT. The gastric cancer lesion became only a cicatrix with endoscopic examination. For gastric cancer, the availability of mFOLFOX6 was suggested.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Colectomy; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Positron-Emission Tomography; Stomach Neoplasms; Tomography, X-Ray Computed

To compare the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of FOLFOX6 and TLF regimens for advanced gastric cancer.. The clinical data of 81 chemotherapy-naive patients with advanced gastric cancer were analyzed. Of the 81 patients, 41 were treated with FOLFOX6 regimen and 40 with TLF regimen. The patients in FOLFOX6 group received intravenous infusion of L-OHP(100 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at day 1, and continuous intravenous infusion of 5-FU (1200 mg/m2/d) for 22 h at days 1-2, each treatment cycle lasting 14 days. The patients in TCF group received TAX (90 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at days 1-2, and continuous intravenous infusion of 5-FU (400 mg/m2/d) for 22 h at days 1-2, and each treatment cycle also lasted 14 days.. The objective response rates were 48.8% in FOLFOX6 group and 50.0% in TLF group (P=0.962). The median TTP in the two groups was 6.30 months and 6.50 months (P=0.958), with median survival time of 9.80 months and 10.70 months (P=0.578), respectively. The most frequent adverse events were nausea, vomiting and hematologic toxicities. The incidences of grade III-IV leucopenia and neutropenia were lower in FOLFOX6 group than in TLF group, but the difference was not statistically significant (12.2% vs 30.0%, P=0.112; 14.6% vs 32.5%, P=0.126). Three patients in FOLFOX6 group developed intestinal obstruction during the chemotherapy.. Both FOLFOX6 and TLF regimens are effective in treating advanced gastric cancer and the toxicities can be tolerated.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Taxoids

Gastric outlet obstruction (GOO) caused by unresectable gastric cancer is a challenging aspect of patient care. There have been no reports involving patients with obstructing gastric cancer and several incurable factors curatively treated by multimodal treatments.. We report a case of 55-year-old man who was diagnosed with a poorly differentiated adenocarcinoma in the pre-pyloric antrum with GOO by gastroscopy. An abdominal computed tomography (CT) scan revealed thickening of the gastric wall and adjacent fat infiltration, and a large amount of food in the stomach suggesting a passage disturbance, enlarged lymph nodes along the common hepatic and left gastric arteries, and multiple hepatic metastases. The serum carcinoembryonic antigen (CEA) level was 343 ng/ml and the carbohydrate antigen (CA) 19-9 level was within normal limits. The patient underwent a laparoscopic gastrojejunostomy for palliation of the GOO. On the 3rd and 12th days after surgery, he received intraperitoneal chemotherapy with 40 mg of docetaxel and 150 mg of carboplatin. Simultaneously, combined chemotherapy with 85 mg/m2 of oxaliplatin for the 1st day and 600 mg/m2 of 5-FU for 2 days (FOLFOX regimen) was administered from the 8th post-operative day. After completion of nine courses of FOLFOX, the patient achieved a complete response (CR) with complete disappearance of the primary tumor and the metastatic foci. He underwent a radical subtotal gastrectomy with D3 lymph node dissection 4 months after the initial palliative surgery. The pathologic results revealed no residual primary tumor and no lymph node metastasis in 43 dissected lymph nodes. He has maintained a CR for 18 months since the last operation.. Combination chemotherapy with systemic and intraperitoneal chemotherapy following laparoscopic bypass surgery showed marked efficacy in the treatment for unresectable advanced gastric cancer with GOO.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Gastric Bypass; Gastric Outlet Obstruction; Humans; Injections, Intraperitoneal; Laparoscopy; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Palliative Care; Prognosis; Stomach Neoplasms

The patient was a 59-year-old man who was hospitalized at our department for intestinal obstruction. Contrast enhanced abdominal CT showed a rectosigmoid tumor invading the left pelvic wall and multiple metastatic hepatic tumors. Colonoscopy showed a type-2 cancer in the rectosigmoid region. The patient underwent sigmoid colostomy 3 days after admission. Postoperative upper gastrointestinal endoscopy showed a type 3 cancer in the fornix. From the above findings, the patient was diagnosed with unresectable gastric and rectosigmoid cancers with multiple hepatic metastases, and systemic chemotherapy was initiated. The first line treatment was two courses of S-1, but it was discontinued due to PD. FOLFIRI was begun as the second line treatment. After 5 courses of FOLFIRI, upper gastrointestinal endoscopy showed a marked reduction in tumor size. Twelve courses of FOLFIRI chemotherapy were performed in total. Subsequently, 11 courses of mFOLFOX6 and 1 course of RPMI were performed, but the patient died from carcinomatous peritonitis. However, the gastric lesion had been controlled well after the second line treatment. The findings of the present study suggested that FOLFIRI could be an effective treatment for unresectable multiple advanced cancers of the stomach and colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Sigmoid Neoplasms; Stomach Neoplasms

Chemotherapy and radiotherapy are approved in clinical practice of adjuvant treatment of gastric carcinoma. In present study, we retrospectively evaluated the efficacy and tolerability of an adjuvant treatment protocol including bi-weekly cisplatin, infusional 5-fluorouracil (5-FU) and folinic acid followed by continuous 5-FU infusion during radiotherapy.. Between May 2005 and Dec 2008, 65 curatively resected gastric and gastroesophageal junction adenocarcinoma patients (stage III in 38 and stage IV M0 in 27) received chemotherapy including 50 mg/m2 cisplatin, 200 mg/m2 iv folinic acid, 5-FU 400 mg/m2 iv bolus followed by 5-FU 1600 mg/m2 46h-continuous infusion (CFF) bi-weekly. After 4 cycles of CFF, concomitant 200 mg/m2/day continuous infusion 5-FU and 4500 cGy radiotherapy were administered for 5 weeks. After this chemoradiotherapy an additional 4 cycles of CFF were given.. The median follow-up was 15 (6-36) months. Fifty seven (87.7%) patients completed at least 90% of the planned treatment. Median disease free survival was 18 months (95% CI:13.9-22.0) and median overall survival was 19 months (95% CI:15.2-22.8). Common adverse events of all grades were nausea and vomiting (53.8%), leucopenia (42.6%), anemia (30.7%) and diarrhea (20%). The most common grade 3 and 4 toxicities were leucopenia (9.2%), anemia (7.6%), febrile neutropenia (6.1%) and diarrhea (4.6%).. Bi-weekly CFF chemotherapy followed by continuous 5-FU infusion during radiotherapy is an effective and tolerable regimen for locally advanced operated gastric and gastroesophageal junction adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Risk Factors; Stomach Neoplasms; Survival Rate; Treatment Outcome

Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates.. Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m(2), folinic acid 200 mg/m(2), and fluorouracil 400 mg/m(2) were given on day 1, immediately followed by fluorouracil 2,400 mg/m(2) 46 h continuous infusion (simplified FOLFIRI), every 2 weeks.. Between June 2002 and May 2003, 28 patients were treated. Median age was 57 years (range 38-68). Most patients had a distal primary (90%), and metastatic disease (71%). Partial response was obtained in six patients (21%, 95% CI 8-41) and stable disease in eight (21%, 95% CI 13-41). Among the six responsive patients three were refractory to docetaxel. At a median follow-up of 2.9 years median time to progression was 4 months (95% CI: 2-5), and median overall survival was 5 months (95% CI 4-9). Toxicity was mild, without treatment-related deaths or life-treating adverse events.. Simplified FOLFIRI was moderately active and well tolerated in unselected patients with MGC pre-treated with cisplatin-based chemotherapy. Its role in patients refractory to taxanes is promising and warrants further investigation.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Quality of Life; Stomach Neoplasms; Survival Rate; Treatment Outcome; Young Adult

Gastric carcinoma is often diagnosed at UICC stage 3 b or 4. R0 resection can be achieved only in very few such cases. Even for these patients the 5-year survival rate is less than 5 %. Surgical palliation is traditionally reserved for the treatment of severe tumour complications not responding to other forms of treatment.. We report on 21 patients who underwent palliative resection for gastric carcinoma at our institution between 2004 and 2007. Ten of these were assigned to palliative surgical treatment pre-operatively while this choice was made for 11 patients on the grounds of the intra-operative findings. We performed 17 gastrectomies, 3 proximal gastric resections and one distal gastric resection.. It has been shown that the patients have an improved overall survival time as compared to patients who received non-surgical treatment. The perioperative risk was reasonable when patients were carefully selected. Median survival for resected patients was 16 months. 80 % of patients were alive after 6 months and approximately 60 % of patients were alive after 12 months. The perioperative mortality was 0 % with a mean hospital stay of 12 days. All patients were discharged home with proper bowel passage and analgesia as individually required.. We are convinced that palliative gastric resection provides a pronounced survival benefit over any other palliative treatment options. Patients also have an improved quality of life.

Topics: Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Chemotherapy, Adjuvant; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Laparotomy; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Palliative Care; Patient Selection; Postoperative Care; Quality of Life; Stomach; Stomach Neoplasms; Time Factors

Neoadjuvant therapy is applied to improve the prognosis associated with advanced gastric cancer. Only patients with a major response seem to have a survival benefit. Predictive markers to allow individualisation of treatment could be helpful. We examined the association of survivin protein expression with histopathologic response to neoadjuvant chemotherapy and prognosis in patients with gastric cancer.. Forty patients with gastric cancer received neoadjuvant chemotherapy. Afterwards, 38 patients underwent total gastrectomy, while 2 patients received definitive chemotherapy because of tumour progression. Histomorphologic regression was defined as major response when resected specimens contained <10% tumour cells. Intratumoural survivin expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters.. The pre- and post-therapeutic intratumoural survivin protein expression was not associated with histomorphologic regression. Post-therapeutic survivin expression did not have prognostic impact. A significant association was detected between pre-therapeutic survivin levels and prognosis: patients with a higher survivin protein expression showed a significant survival benefit. In multivariate analysis pre-therapeutic survivin expression was characterised as an independent prognostic marker, besides pN-status and histopathologic regression.. The pre-therapeutic survivin protein expression seems to be an independent prognostic marker in the multimodality treatment of advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Gastrectomy; Gene Expression Profiling; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins; Leucovorin; Male; Microtubule-Associated Proteins; Middle Aged; Neoadjuvant Therapy; Stomach Neoplasms; Survivin

Because treatment of advanced gastric cancer (AGC) patients after failure with first-line chemotherapy remains controversial, we performed this retrospective analysis based on the data obtained from 1455 patients registered in a first-line treatment cohort with respect to receiving or not receiving subsequent chemotherapy.. The decision for administering second-line chemotherapy was, in most cases, at the discretion of the physician. Seven-hundred twenty-five (50%) received second-line chemotherapy after first-line failure. Univariate and multivariate analyses were performed on the recognized baseline parameters for survival.. At the time of initiating second-line chemotherapy, the patients' median age was 56 years (range, 22 to 86) and 139 (19%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. Seven (1%) complete and 108 (15%) partial responses to second-line chemotherapy were observed for an overall response rate of 16% (95% confidence interval [CI], 13 to 19%). The median progression-free and overall survivals, calculated from the start of second-line chemotherapy, were 2.9 months (95% CI, 2.6 to 3.3) and 6.7 months (95% CI, 5.8 to 7.5), respectively. Multivariate analysis revealed that low baseline hemoglobin level (hazard ratio [HR], 0.74; 95% CI 0.61-0.90) and a poor performance status (HR, 0.66; 95% CI, 0.52-0.83) were independent negative prognostic factors for overall survival.. Performance status, along with baseline hemoglobin level, could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy for AGC.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Survival Rate; Taxoids; Treatment Outcome; Young Adult

Adjuvant radiochemotherapy improves survival of patients with advanced gastric cancer. We assessed in two sequential cohorts whether improved radiotherapy technique (IMRT) together with intensified chemotherapy improves outcome vs. conventional three-dimensional conformal radiotherapy (3D-CRT) and standard chemotherapy in these patients while maintaining or reducing renal toxicity.. Sixty consecutive patients treated for gastric cancer either with 3D-CRT (n = 27) and IMRT (n = 33) were evaluated. More than 70% had undergone D2 resection. Although there was a slight imbalance in R0 status between cohorts, N+ status was balanced. Chemotherapy consisted predominantly of 5-fluorouracil/folinic acid (n = 36) in the earlier cohort and mostly of oxaliplatin/capecitabine (XELOX, n = 24) in the later cohort. Primary end points were overall survival (OS), disease-free survival (DFS), and renal toxicity based on creatinine levels.. Median follow-up (FU) of all patients in the 3D-CRT group was 18 months and in the IMRT group 22 months (median FU of surviving patients 67 months in the 3D-CRT group and 25 months in the IMRT group). Overall median survival (and DFS) were 18 (13) months in the 3D-CRT group and both not reached in the IMRT group (p = 0.0492 and 0.0216). Actuarial 2-year survival was 37% and 67% in the 3D-CRT and IMRT groups, respectively. No late renal toxicity >Grade 2 (LENT-SOMA scale) was observed in either cohort.. When comparing sequentially treated patient cohorts with similar characteristics, OS and DFS improved with the use of IMRT and intensified chemotherapy without signs of increased renal toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Capecitabine; Chemotherapy, Adjuvant; Cohort Studies; Creatinine; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Kidney; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Radiation Injuries; Radiotherapy Dosage; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Stomach Neoplasms

The BCL2 (bcl-2)family of genes is highly involved in the apoptotic mechanisms. We have recently discovered and cloned a novel member of the same family, BCL2L12. The aim of this study was to investigate the modulations in the BAX, BCL2 and BCL2L12 mRNA levels in gastric cancer cells, after their treatment with the anticancer drugs 5-fluorouracil and irinotecan as well as the antioxidant substance leucovorin. AGS gastric cancer cells were examined for their sensitivity to antineoplastic drugs and/or antioxidants using the MTT assay. Total RNA was extracted and reverse transcribed into cDNA. A highly sensitive quantitative real-time PCR method for the mRNA quantification was developed using the SYBR Green chemistry. GAPDH was used as a housekeeping gene. Relative quantification analysis was performed using the comparative threshold cycle method. Treatment of AGS cells with 5-fluorouracil (5 microM), leucovorin (10 microM), a combination of the latter and, eventually, irinotecan (1 microM) for 3 time periods (24, 48 and 72 h), resulted in significant modulations of the BCL2, BAX and BCL2L12 mRNA levels compared with the untreated cells. Our experimental data demonstrate that the molecular profile mainly of BCL2 and BCL2L12 genes may serve as a new potential molecular biomarker predicting treatment response in gastric cancer cells.

Topics: Antineoplastic Agents; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Camptothecin; Cell Line, Tumor; Drug Therapy, Combination; Fluorouracil; Gene Expression; Humans; Irinotecan; Leucovorin; Muscle Proteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Stomach Neoplasms

A 75-year-old man was diagnosed with gastric cancer (UL post c0- II c (c T1N0) and M-less ctype II (cT2N0)) and rectal cancer (Rb ctype II (cT2N1) with multiple lung metastases (M1). The patient was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). Chest and abdominal CT scan revealed that multiple lung metastases and abdominal lymph node metastases were obviously reduced in size. The primary lesion of the rectum almost disappeared on endoscopic examination. As for the lesions of the stomach, the UL post c0- II c lesion completely disappeared, and the M-less ctype II lesion was reduced remarkably. Thus, a significant reduction of the tumors was observed. This case suggests that mFOLFOX6 regimen can be an option for gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Stomach Neoplasms; Vitamin B Complex

Insulin-like growth factor-1 receptor (IGF-1R) displays a key role in tumor transformation and metastasis. It also makes tumor cells more resistant to chemotherapy. The aim of this study was to investigate the correlation between IGF-1R and multidrug resistance-associated protein-1 (MRP-1), and the clinical significance of their expression in gastric carcinoma (GC).. IGF-1R and MRP-1 expressed in 113 specimens were detected by immunohistochemistry. The correlation between IGF-1R and MRP-1 expression was determined. In addition, the association of their expression with clinicopathological features and survival data of GC was also analyzed.. IGF-1R (75.2%) and MRP-1 (69.0%) were frequently expressed in GC. IGF-1R was associated with tumor size, quantity of stroma, depth of wall invasion, lymph node metastasis, TNM stages and differentiation status of GC (p < 0.05). MRP-1 was associated with tumor size, quantity of stroma, lymph node metastasis, distant metastasis and TNM stages (p < 0.05). IGF-1R over-expression positively correlated with MRP-1 over-expression (rp = 0.39, p < 0.01). IGF-1R and MPR-1 over-expression were correlated with poor prognosis of GC (p < 0.01). 102 patients receiving adjuvant FOLFOX-4 chemotherapy who co-expressed IGF-1R/MRP-1 had poor prognosis (p < 0.05).. The levels of co-expression of IGF-1R/MRP-1 in GC may predict the therapeutic effect of chemotherapy and prognosis of GC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Multidrug Resistance-Associated Proteins; Prognosis; Receptor, IGF Type 1; Stomach Neoplasms; Survival Rate

Although peritoneal dissemination of gastric cancer is common and often causes deterioration of the patient's condition and quality of life (QOL), these patients are usually excluded from clinical trials. We retrospectively investigated the clinical benefit and toxicity of sequential methotrexate and 5-fluorouracil (MTX/5FU) therapy for patients with peritoneal dissemination.. The subjects were 31 patients with severe peritoneal dissemination of gastric cancer who were treated with MTX/5FU. The treatment schedule comprised weekly administration of MTX (100 mg/m(2)) followed by 5FU (600 mg/m(2)). Leucovorin (10 mg/m(2)) was administered six times, every 6 h, starting 24 h after MTX administration.. The median survival time was 255 days, and the median progression-free survival was 127 days. Of the 21 patients with measurable lesions, 4 (19%) patients achieved a partial response. Ascites volume decreased markedly in 14 (54%) of the 26 patients with ascites. Seventeen patients had adequate oral intake, but the other 14 patients had required nutritional support before treatment. The median dripinfusion free survival was 100 days in the former 17 patients, and oral intake improved in 3 (21%) of the latter 14 patients. Grade 3 or 4 neutropenia was observed in 26% of the patients and anemia was observed in 45%. The grade 3 nonhematological toxicities were vomiting (6%) and fatigue (10%). Early death, within 30 days of the last administration of MTX/5FU, occurred due to disease progression in 2 patients, but there were no treatment-related deaths.. MTX/5FU chemotherapy may be effective in treating peritoneal dissemination of gastric cancer and might improve the patient's condition in terms of reducing ascites and improving oral intake.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneal Neoplasms; Quality of Life; Retrospective Studies; Severity of Illness Index; Stomach Neoplasms; Survival Rate; Treatment Outcome

The patient was a 51-year-old male diagnosed with gastric cancer in July 1999 by endoscopic examination, revealing multiple liver metastasis with abdominal computed tomography (CT). The serum levels of alpha-fetoprotein (AFP)were determined to be 91 ng/mL, and tumors were histopathologically identified as AFP-producing gastric cancer by immunohistological staining. We started combination chemotherapy with 5-fluorouracil (5-FU), Leucovorin (LV), etoposide (VP-16) and cis-diaminedichloroplatinum (CDDP) (designated as FLEP)in August 1999. The serum AFP value was normalized after two courses, and the liver metastases disappeared. The primary gastric tumor became a ulcer, and disappearance of the cancer was confirmed histologically. We continued adjuvant chemotherapy with S-1 as an outpatient. In April 2000, there was no sign of the liver metastases, but endoscopic examination showed IIc-like lesion in the stomach. We performed 2 courses of FLEP, but the tumor did not disappear. He underwent total gastrectomy with D2 dissection in June 2001. The pathological diagnosis was por 1, ss, ly2, v1, n(1+). He was still alive with no sign of recurrence 84 months after surgery. We experienced this AFP-producing gastric cancer in which CR was possible by FLEP. There was no recurrence after total gastrectomy for local recurrence.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Etoposide; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

To observe the therapeutic response of advanced gastric cancer with severe lymph nodes metastasis to FLEEOX regimen neoadjuvant chemotherapy that combined arterial and venous administration.. Neoadjuvant chemotherapy was administered to 32 cases of gastric cancer with advanced abdominal lymph nodes metastases from January 2007 to October 2008. Of the 32 patients, 28 had severe local lymph nodes metastasis, such as No.3, 7, 9, 12 lymph nodes metastasis, one patient had No.16 lymph nodes metastasis, and the other 3 patients had both regional and No.16 lymph nodes metastasis under CT scan. Neoadjuvant chemotherapy was administered as follows: 5-Fu 370 mg/m(2), intravenous drip, day 1 - 5; Leukovorin 120 mg, intravenous drip, day 1 - 5; oxaliplatin 150 mg/m(2), epirubicin 30 mg/m(2) and epotoside 70 mg/m(2), intravascular infusion through arteria gastrica sinistra, day 6 and 20. The protocol was repeated every five weeks for two or three courses. After 2 or 3 cycles of chemotherapy, abdominal CT was taken to evaluate the radiological therapeutic response and calculate the reductive rate of the tumor.. The general conditions and symptoms was improved significantly in all the patients. Four cases got complete response (CR), 24 got partial response (PR) and 4 got no change under CT scan. For the 32 case, the radiological response rate (CR + PR) was 87.5%(28/32). Thirty patients underwent subtotal or total gastrectomy, even combined organ resection, with D2 or D2 + alpha lymphadenectomy.. The FLEEOX regimen which combines arterial and venous administration carries a satisfactory therapeutic effect in advanced gastric cancer with severe lymph nodes metastasis. The combined routes of drug administration may improve the effects of neoadjuvant chemotherapy in stomach cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Treatment Outcome

To evaluate the efficacy and safety of FOLFOX7 scheme as neoadjuvant chemotherapy in patients with stage III gastric adenocarcinoma.. From May 2005 to May 2007, 27 patients with stage III gastric adenocarcinoma were given neoadjuvant chemotherapy with FOLFOX7 scheme. Gastroscopy, endoscopic ultrasonography, abdominal B ultrasonography and abdominal CT was taken before chemotherapy and after 2 - 4 cycles of neoadjuvant chemotherapy to evaluate the objective response rate of the tumor. Then operations were carried out and the pathological responses was evaluated in those cases. The safety, objective response rate and pathological rate of neoadjuvant chemotherapy was assessed according to NCI-CTC v3.0, RECIST 2000, and the criteria established by Japanese Research Society for Gastric Cancer, respectively. R0 resection rate and surgery-related complications was also assessed in this group.. The treatment was well tolerated, no grade 3 - 5 toxicity was observed. Complete response was obtained in 1 case, and partial response in 18 patients, overall response rate was 70.4% (19/27). Twenty-six patients received operation and R0 resection rate was 88.4% (23/26); no patient died in the perioperative period. The pathological response rate of patients had R0 excision was 60.9% (14/23).. FOLFOX7 scheme as neoadjuvant chemotherapy for selected patients with stage III gastric adenocarcinoma can be well tolerated, it could induce tumor down-staging and improve R0 resection rate, although the long term efficacy remains to be evaluated.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Prospective Studies; Stomach Neoplasms; Treatment Outcome

To evaluate the efficacy and toxicity of oxaliplatin-based regimen in patients with advanced or metastatic gastric/esophagogastric junction cancer (AGC).. The clinicopathological data of a total of 180 patients with AGC were retrospectively analyzed. Responses was evaluated by RECIST criteria, and toxicity were assessed according to the NCI-CTC AE version 3.0.. 155 patients received mFOLFOX regimen, and 25 patients received regimens of mEOF and CapOX, with a total chemotherapy of 717 cycles with a median of 3 cycles. The therapeutic response was evaluated in 150 patients, showing response rate (RR) of 30.0% and disease control rate (DCR) of 74.0%. The response was evaluated in 103 of 124 patients who received the therapy as 1st line, with RR of 34.0%, DCR of 74.8%, and overall survival of 11.3 months. The major grade III/IV adverse events were leucocytopenia (14.4%), neutropenia (17.8%), thrombocytopenia (3.8%), nausea/vomiting (8.9%), and peripheral neuropathy (2.2%), with no treatment related death.. Oxaliplatin-based regimen is active and well tolerated in patients with advanced or metastatic gastric/esophagogastric junction cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer.. Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m(2) and LV 100 mg/m(2) (2-h intravenous infusion) followed by 5-FU 2,400 mg/m(2) (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles.. Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32-76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths.. The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Survival Analysis; Treatment Outcome

To detect the nuclear factor kappa B (NF-kappaB) condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-kappaB activation and survival of these patients after chemotherapy.. Expression of NF-kappaB-p65 was determined by immunohistochemical analysis. Activity of NF-kappaB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay. Kaplan-Meier survival analysis was performed to show the relation between NF-kappaB and progression-free survival (PFS) or overall survival (OS) of the patients.. The positive expression rate of NF-kappaB-p65 in 60 gastric cancer tissue samples was 76.7% (46/60). The expression of NF-kappaB-p65 was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic mobility shift assay (EMSA) analysis showed a strong activation of NF-kappaB in cancer tissue samples. A survival difference was found in NF-kappaB-p65 positive and negative patients. NF-kappaB-p65 expression was negative in cancer tissue samples (n=14). PFS was 191.40+/-59.88 d and 152.93+/-16.99 d, respectively, in patients with positive NF-kappaB-p65 expression (n=46) (P=0.4028). The survival time of patients with negative and positive NF-kappaB-p65 expression was 425.16+/-61.61 d and 418.85+/-42.98 d, respectively (P=0.7303). Kaplan-Meier analysis showed no significant difference in PFS or OS. The 46 patient tissue which positive NF-kappaB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89+/-75.94 d and s 352.37+/-41.32 d, respectively (P=0.0165).. NF-kappaB is activated in gastric carcinoma tissue, which is related to the OS after chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma; Disease-Free Survival; Electrophoretic Mobility Shift Assay; Female; Fluorouracil; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Paclitaxel; Stomach Neoplasms; Time Factors; Transcription Factor RelA; Treatment Outcome

To compare the efficacy and tolerability of the regimen FOLFOX [1eucovorin (LV), 5-fluorouracil (5-Fu) and oxaliplatin] and the regimen PLF (Paclitaxel, leucovorin and 5-Fu) for treatment of advanced gastric adenocarcinoma.. We retrospectively studied the clinical data of 132 patients with stage IV gastric adenocarcinoma treated by FOLFOX (group A, n=60) or PLF (group B, n=72). The tumor response rate, toxicity, time to progress (TTP) and overall survival (OS) were compared between the two groups.. A total of 544 cycles were administrated in these patients. The overall response rate was 35.0% with FOLFOX regimen and 41.7% with PLF regimen, showing no significant difference between them (P>0.05). The TTP was 6.13-/+1.26 (95%CI, 3.65-8.61) months in group A, and 5.92-/+0.49 (95%CI, 4.97-6.87) months in group B; the OS was 10.67-/+1.55 (95%CI, 7.63-13.71) months in group A, and 10.8-/+3.07 (95%CI, 4.78-16.82) months in group B. Neither TTP or OS showed significant differences between the two groups (P>0.05). Five patients in group A (8.33%) and 8 in group B (11.11%) had grade 3 and 4 leukopenia. The non-hematological toxicities were mostly mild, including nausea, vomiting, stomatitis, diarrhea and alopecia. The main adverse effects were grade 1 or 2 sensory neuritis in FOLFOX group, and alopecia in PLF group, without significant difference between the two groups (P<0.05).. Both FOLFOX and PLF can serve as effective first-line treatment of stage IV gastric adenocarcinoma with good tolerance.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

To evaluate the toxicity and efficacy of combination regimen with oxaliplatin plus fluorouracil and leucovorin(FOLFOX) as post-operative adjuvant chemotherapy in local advanced gastric cancer.. Twenty-five gastric cancer patients, 2 at the stage II, 17 at the stage III, and 6 at the stage IV received the FOLFOX regimen after surgery: intravenous infusion of oxaliplatin 85 mg/m2 for 2 h on day 1, intravenous infusion of leucovorin 200 mg/m2 for 2 h on days 1-2, and intravenous bolus injection of 5-fluorouracil (5-FU) 400 mg/m2 on days 1-2, and continuous infusion of 5-FU 600 mg/m2 for 22 h on days 1-2; and this regimen was repeated every 2 weeks. The effect and adverse reactions were recorded.. The median disease free survival time and overall survival time were 26.0 months and 38.0 months respectively. The frequent grade 3/4 toxicity of the FOLFOX regimen included: neutropenia (12.4%), thrombocytopenia (8.2%), and nausea (7.5%).. The post-operative adjuvant chemotherapy of FOLFOX regimen has expectable efficacy in treatment of gastric cancer with light and well tolerable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Young Adult

There are different types of skin changes associated with internal malignancy. One type is the skin involvement as a result of cutaneous metastasis from an internal tumor. The skin is an uncommon site for distant metastasis; when it is present the most common sources are breast, lung, and colon. Metastasis generally occurs after an internal malignancy had been discovered and signifies disseminated disease with a poor prognosis. We report an exuberant and rare case of cutaneous metastasis from gastric adenocarcinoma as the first sign of this serious visceral cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cachexia; Carcinoma, Signet Ring Cell; Etoposide; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Skin Neoplasms; Spinal Neoplasms; Stomach Neoplasms; Treatment Failure

To investigate the pre- and post-chemotherapy expression levels of Th1 and Th2 type cytokines in peripheral blood CD4(+) T lymphocytes, the changes of Th1/Th2 ratio and their clinical significance in patients with gastric cancer.. The levels of specific cytokines in 60 gastric cancer patients were detected by flow cytometry before and after chemotherapy with FOLFOX4.. The level of IFN-gamma from peripheral blood CD4(+) T lymphocytes after chemotherapy in the whole group of gastric cancer patients was 11.4% +/- 5.0%, significantly higher than that (9.5% +/- 3.4%) before chemotherapy (P < 0.05). The level of IL-10 after chemotherapy was 3.6% +/- 1.2%, significantly lower than that (4.2% +/- 1.8%) before chemotherapy (P < 0.05). The ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 3.4 +/- 1.0 versus 3.4 +/- 1.6 before chemotherapy, without significant difference (P > 0.05). Interestingly, the levels of IFN-gamma and TNF-alpha of peripheral blood CD4(+) T lymphocytes in 15 gastric cancer patients who achieved partial response (PR) after chemotherapy were 14.8% +/- 8.0% and 5.9% +/- 2.0%, respectively, both were higher than that (6.9% +/- 2.5% and 4.2% +/- 1.3%) before chemotherapy (both P < 0.05). Furthermore, the ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 4.0 +/- 1.5, significantly higher than 2.5 +/- 1.2 before chemotherapy (P < 0.01).. Effective chemotherapy may reduce the tumor burden and relieve the shift of Th1/Th2 ratio. Improvement in immune function may be a very important therapeutic measure due to poor response of chemotherapy in gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CD4-Positive T-Lymphocytes; Female; Fluorouracil; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Remission Induction; Stomach Neoplasms; Th1 Cells; Th2 Cells; Tumor Burden; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Treatment Outcome

There are no reliable prognostic markers that identify gastric cancer patients who may benefit from adjuvant chemoradiation therapy. E2F-1 was shown to be associated with radiosensitivity and chemosensitivity in certain tumor types. Therefore, we analyzed expression and prognostic significance of E2F-1 along with thymidylate synthase (TS) in R(0)-resected gastric adenocarcinoma patients, who underwent adjuvant chemoradiation therapy with 5-fluorouracil (5-FU) and leucovorin.. The chemosensitivity to 5-FU and radiosensitivity were tested in three E2F-1-overexpressed gastric cancer cell lines in vitro. The expressions of TS and E2F-1 were analyzed in 467 R(0)-resected primary gastric cancer patients, who received adjuvant chemoradiation therapy with 5-FU and leucovorin using tissue microarray.. The E2F-1 immunopositivity rate was 22.2% (103 of 465 samples) with a cutoff value of 5% immunoreactivity, whereas the TS-positive expression occurred in 19.0% of the 463 tumors tested. Using stepwise Cox proportional hazards regression modeling, multivariate analyses showed that the E2F-1 immunopositivity predicted more favorable survival as compared with the E2F-1 immunonegativity with borderline statistical significance [P = 0.050, hazard ratio (HR) = 0.702, 95% confidence interval, 0.487, 1.013]. However, the E2F-1 immunopositivity did not retain its statistical significance at multivariate analysis for predicting disease-free survival (data not shown, P = 0.270), but stage was the only influential factor for disease-free survival in stages IB to IV (M(0)) patients (P < 0.001). TS immunopositivity did not influence survival (P = 0.459) or disease-free survival (P = 0.447).. E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Chemotherapy, Adjuvant; Combined Modality Therapy; Digestive System Surgical Procedures; Disease-Free Survival; E2F1 Transcription Factor; Female; Fluorouracil; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Prognosis; Radiotherapy, Adjuvant; Stomach Neoplasms; Survival Analysis; Thymidylate Synthase; Tissue Array Analysis; Treatment Outcome

The patient was a 66-year-old woman who underwent upper gastrointestinal endoscopy as part of a detailed examination because of loss of appetite and anemia, and type 2 gastric cancer was detected on the greater curvature in the pyloric area. Abdominal ultrasonography and CT revealed lymph node enlargement around the pyloric area and multiple liver metastases in both lobes of the liver. Curative resection was judged to be impossible, and oral S-1 therapy was started. However, no efficacy was observed even after the completion of three courses, and especially because of the rapid increase in the size of the liver metastases, treatment was switched to combination therapy consisting of a continuous hepatic artery infusion of 5-FU+Leucovorin (day 1-7) and weekly PTX for 3 consecutive weeks (day 8, 15, 22) followed by a 1-week rest. The tumor marker levels decreased rapidly, and at the end of 4 courses marked regression of the primary tumor and lymph node metastases as well as of the metastatic foci in the liver was observed. Adverse events have been mild, and at present, 6 months after the switch in treatment, good QOL has been maintained, and treatment is continuing. This method appears to be an effective treatment strategy for unresectable advanced gastric cancer complicated by liver metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Female; Fluorouracil; Gastroscopy; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Neoplasm Staging; Paclitaxel; Stomach Neoplasms; Time Factors; Tomography, X-Ray Computed

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Epirubicin; Fluorouracil; Gastrectomy; Humans; Italy; Leucovorin; Randomized Controlled Trials as Topic; Stomach Neoplasms; Treatment Outcome; United Kingdom

Molecular markers involved in DNA repair can help to predict survival in gastric cancer patients treated with 5-FU plus platinum chemotherapy. Excision repair cross-complementing 1 (ERCC1) and thymidylate synthase (TS) mRNA expression levels were assessed in advanced gastric cancer tumour samples using real-time quantitative PCR in 76 patients treated with a modified FOLFOX (biweekly oxaliplatin plus 5-FU and folinic acid) regimen. Median survival time in patients with low ERCC1 levels was significantly longer than in those with high levels (15.8 vs 6.2 months; P<0.0001). Patients with high TS levels had longer survival than those with low levels (12.2 vs 10.1 months; P=0.01). Forty-eight patients with low ERCC1 and high TS levels had a median survival of 16.1 months (P<0.0001). The hazard ratio for patients with high ERCC1 expression was 9.4 (P<0.0001). In patients with high mRNA levels of ERCC1, alternative chemotherapy regimens should be considered.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Thymidylate Synthase

To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC).. Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)).. Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Grade > or =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively.. This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Survival Rate; Time Factors

We retrospectively assessed the combination of biweekly irinotecan with 5-fluorouracil (5-FU), and leucovorin (LV) as salvage chemotherapy in patients with advanced gastric cancer (AGC) previously treated with fluoropyrimidine (F), platinum (P), and taxane (T).. Between October 2003 and February 2006, all 131 patients with AGC were treated with irinotecan (150 mg/m(2) on day 1), along with either FOLFIRI-1 (ie, LV (20 mg/m(2) bolus) before 5-FU (1000 mg/m(2) continuous infusion over 6-hour) on days 1-2), or FOLFIRI-2 (ie, LV (20 mg/m(2) bolus) before 5-FU (400 mg/m(2) bolus) followed by 22-hour continuous infusion of 600 mg/m(2) on days 1-2), or FOLFIRI-3 (ie, 5-FU (400 mg/m(2) bolus) followed by 46-hour continuous infusion of 2400 mg/m(2) 5-FU and 100 mg/m(2) LV). Cycles were repeated every 2 weeks.. The median age of the patients was 52 years (range, 19-70 years). Patients received a median of 4 cycles of chemotherapy (range, 1-21 cycles). Of the 97 patients with measurable disease, 1 (1.0%) achieved a complete response, and 11 (11.3%) achieved partial responses, making the overall response rate 12.3%. The median time to progression (TTP) was 2.2 months (95% CI, 1.9-2.6 months) and the median overall survival (OS) was 6.2 months (95% CI, 5.6-6.9 months). Good performance status (P = 0.046), fewer metastatic sites (P < 0.001), and longer time to progression of previous chemotherapy (P = 0.006) were independent prognostic factors affecting OS. OS was longer with the FOLFIRI-1 regimen but not with statistical significance (P = 0.064). The treatments were generally well tolerated.. In actual clinical practice, biweekly irinotecan with 5-FU and LV had modest activity and tolerability in AGC patients previously treated with F, P, and T.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Survival Analysis

Currently, there is no standard regimen for advanced gastric cancer. FOLFOX4 regimen [oxaliplatin(L-OHP) with 5-fluorouracil (5-FU)] and DP(O)F regimen [docetaxel (TXT), oxaliplatin (L-OHP)/cisplatin (DDP) with 5-FU] are usually used in treating gastric cancer with satisfactory efficacy. This study was to compare the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of the two regimens for advanced gastric cancer.. Clinical data of 70 chemotherapy-naive patients with advanced gastric cancer were analyzed. Of the 70 patients, 34 were treated with FOLFOX4 regimen, 36 were treated with DP(O)F regimen. The patients in FOLFOX4 group received intravenous infusion of L-OHP (85 mg/m(2)) at Day 1, bolus injection of 5-FU (400 mg/m(2)) at Days 1-2, and continuous intravenous infusion of 5-FU (600 mg/m(2)) for 22 h at Days 1-2; 14 days as one cycle. The patients in DP(O)F group received administration of TXT [20 mg x (m2 x w)(-1)], intravenous infusion of DDP (40 mg/m(2)) at Days 2-3 or L-OHP (100 mg/m(2)) at Day 2, and intravenous infusion of 5-FU (500 mg/m(2)) at Days 1-5; 21 days as one cycle.. The objective response rates were 45.4% in FOLFOX4 group and 52.8% in DP(O)F group (P=0.628). The median TTP was 5.27 months in FOLFOX4 group and 4.70 months in DP(O)F group (P=0.848). The median survival time was 8.97 months in FOLFOX4 group and 12.17 months in DP(O)F group (P=0.095). The most frequent adverse events were nausea, vomit and hematologic toxicities. The occurrence rates of grade III-IV leukopenia and neutropenia were significantly lower in FOLFOX4 group than in DP(O)F group (11.8% vs. 36.1%, P=0.025; 17.6% vs. 41.7%, P=0.038). One patient in FOLFOX4 group died of liver function failure.. Both FOLFOX4 and DP(O)F regimens are effective in treating advanced gastric cancer. The hematologic toxicities of DP(O)F regimen are worse than those of FOLFOX4 regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Taxoids

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Middle Aged; Stomach Neoplasms

Gastric cancer is often diagnosed in advanced stage (AGC) and in elderly patients. Current chemotherapies induce severe toxicity and are difficult to deliver. Some authors have shown the activity and safety of oxaliplatin with various 5-fluorouracil (FU) and leucovorin (LV) infusions in AGC. The aim of our study was to evaluate the feasibility of the FOLFOX-4 regimen in elderly patients with AGC. From 6/2003 to 7/2005, 33 patients (median age 74 years, range 66-79 years) were enrolled into the study. 31 patients were assessable for the safety analysis and for response. We recorded complete response in 4 patients (13%), partial response in 6 patients (19%), 9 (29%) stable disease and 12 progressive disease for an overall response rate of 32% (95% CI, 16% to 48%). At median follow-up of 20 months the median time to progression was 6.4 months. The therapy was well tolerated, the main G1/2 toxicities were nausea, vomiting and diarrhea. Only 2 patients suffered from severe vomiting. Severe hematologic toxicities were uncommon. Anemia G3 was recorded in 3 patients, neutropenia G3 in 6 patients and febrile neutropenia in 1 patient. G1 and G2 neurotoxicity were a common event while G3 sensorial neuropathy was not reported. We conclude that although our patients were elderly and most had a PS 2, the regimen was manageable, easy to deliver, well accepted by the patients and active.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Safety; Stomach Neoplasms

The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy.. The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry.. The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037).. Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Follow-Up Studies; Glutathione S-Transferase pi; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Thymidylate Synthase; Time Factors; Treatment Outcome

Docetaxel, capecitabine and 5-fluorouracil have been shown to be active in the treatment of metastatic gastric adenocarcinoma. Consistent with this finding, the aim of this study was to test this combination in a clinical trial. Forty-one patients with metastatic gastric adenocarcinoma and a median age of 64 years were recruited for the study. The treatment was based on the administration of docetaxel 60 mg/m2 every 4 weeks, leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus, and capecitabine 1000 mg/m2 twice daily on days 1 and 2 every 2 weeks. Patients achieving a clinical benefit were treated, as maintenance immunotherapy, with low-dose interleukin-2 and 13-cis-retinoic acid. The primary end point of this phase II study was the response rate. The secondary end points relied on the evaluation of the immunological parameters, toxicity, and progression-free survival and overall survival. The overall response rate in the 41 evaluable patients was estimated to be 49%. Median progression-free and overall survival was 9.5 and 21.1 months, respectively. Grade 3 and 4 hematological toxicities were neutropenia and thrombocytopenia in 44 and 5% of patients, respectively. A sustained improvement of evaluated immunological parameters with a negligible toxicity profile was observed in the 27 patients treated with interleukin 1-2/13-cis-retinoic acid. Docetaxel in combination with leucovorin, 5-fluorouracil and capecitabine followed by low-dose interleukin 1-2 and 13-cis-retinoic acid is well tolerated, and shows a significant activity in patients with metastatic gastric adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; CD4-CD8 Ratio; Combined Modality Therapy; Deoxycytidine; Disease Progression; Docetaxel; Dose-Response Relationship, Drug; Endpoint Determination; Female; Fluorouracil; Humans; Immunotherapy; Killer Cells, Natural; Leucovorin; Lymphocyte Count; Male; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms; Survival Analysis; Taxoids; Vascular Endothelial Growth Factor A

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Treatment Outcome

There are many controversies regarding the treatment for primary gastric non-Hodgkin's lymphoma (PGL). We hypothesized that preoperative chemotherapy and extensive surgery would improve patient survival in the treatment of early stage patients with PGL.. Between 1997 and 2001, we prospectively evaluated 10 patients with stage IE and IIE PGL. The histological diagnoses were established by endoscopic biopsies in all cases. All patients received preoperative chemotherapy, i.e. CHOP or MACOP-B. Upon the completion of chemotherapy, the extensive surgery including total gastrectomy, splenectomy, cholecystectomy, and paraaortic lymphadenectomy were performed. The response rates of preoperative chemotherapy and overall survival were analyzed.. All patients were still alive with no signs of recurrence with a median follow-up of 86 months (range, 40 to 102 months) after surgery. In all patients, microscopic examinations did not reveal residual lymphoma cells in the resected stomach or lymph nodes. Chemotherapy-related preoperative complications such as perforation or intestinal bleeding did not occur in any of the cases. Postoperative complications developed in 30% (3/10) of patients and consisted of 2 pancreatic fistulas, 3 intra-abdominal abscesses, and 1 anastomotic leak.. Primary chemotherapy alone without surgery may produce complete remission in Stage IE-IIE PGL.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Preoperative Care; Prospective Studies; Remission Induction; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Stomach Neoplasms

According to the National Comprehensive Cancer Network (NCCN) clinical practice guideline for gastric cancer (2006, the first edition), 5-FU/Leucovorin (LV), 5-FU-based, cisplatin (CDDP)-based, oxaliplatin (L-OHP)-based, taxane-based, and irinotecan (CPT-11)-based, ECF are recommended. We used modified FOLFOX 6 (mFOLFOX 6) for pretreatment, that is oxaliplatin-based chemotherapy, for a patient who had received 5-FU-based, CDDPbased, taxane-based, and CPT-11-based treatment for an unresectable gastric cancer case responding to mFOLFOX 6. A 73-year-old male admitted to our hospital for treatment of advanced gastric cancer was diagnosed to be inoperable. A combination chemotherapy docetaxel and CDDP and S-1 as first-line treatment, CPT-11 and CDDP as second-line treatment, weekly paclitaxel treatment as third-line treatment, and MTX and 5-FU as fourth-line treatment were performed. He had progressed after 5-FU-based, CDDP-based, taxane-based, and CPT-11-based chemotherapy. There are no effective approved drugs for gastric cancer in Japan. Oxaliplatin was reportedly effective for metastatic gastric cancer, but it is still non-approved in Japan. After receiving an explanation of oxaliplatin-based therapy, he gave informed consent. Oxaliplatin-based therapy for this patient was then evaluated and approved under an institutional review board of Higashi Sapporo Hospital. mFOLFOX 6 used for the oxaliplatin-based therapy. After 2 courses of mFOLFOX 6, he showed a partial response. Oxaliplatin-based treatment was thought to be promising for previously CDDP-treated patients with unresectable gastric cancers.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Stomach Neoplasms; Treatment Outcome

This study assessed the value of (18)F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer.. Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria.. Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively).. In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Stomach Neoplasms; Survival Analysis; Tomography, X-Ray Computed

The aim of the study was to evaluate whether the therapy-induced reduction of the (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) maximum standardized uptake value in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab could predict the objective response and outcome early during the treatment.. The study was performed as a part of a phase II trial evaluating cetuximab plus the leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response was evaluated according to the response evaluation criteria in solid tumors (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was assessed according to our own evaluated cutoff value (<35%) after receiver operating characteristic (ROC) analysis.. Twenty of 22 patients had positive baseline 18F-FDG-PET. The best RECIST response was: complete response (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%) were classified as metabolic responders and 8 (40%) as nonresponders. At the median follow-up time of 11 months, median time to disease progression (TTP) and overall survival (OS) for early metabolic responders versus nonresponders were 11 versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively.. The early metabolic response evaluated by 18F-FDG-PET predicted the clinical outcome in this series of patients with advanced gastric cancer treated with chemotherapy plus cetuximab.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Clinical Trials, Phase II as Topic; ErbB Receptors; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Remission Induction; Stomach Neoplasms; Treatment Outcome

Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use.. To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy).. Patients with stage IV gastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed.. Between 2003 and 2006, 29 patients (median age 52.5 years, 69% males) were treated. FOLFOX-4 was given as first line treatment in 65% patients and as second line in 35%. There was a complete response in 4.6%, partial response in 68%, stable disease in 20.6% and progression in 6.8%. Toxicity was observed in 51% of patients, that was hematological and non hematological grade 3/4 in 14%. Median survival was 12.5 months.. FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Pyridines; Stomach Neoplasms; Survival Analysis; Treatment Outcome

To calculate the Normal Tissue Complication Probabilities (NTCP) for the liver, right kidney, left kidney and spinal cord, as well as the global Uncomplicated Tumour Control Probability (UTCP) in gastric cancer patients who underwent a treatment with radiotherapy after radical surgery in our environment.. In April 2000, a postoperative chemotherapy (QT-RT) protocol started in the province of Malaga for Gastric Adenocarcinomas with postsurgical stage II or higher (pT3-4 and/or pN+). This clinical protocol served as a base for our NTCP and UTCP retrospective theorical study. A virtual simulation and a 3D planning were made in all cases. The differential HDV, selected for each patient were obtained for the 4 organs at risk (OR). Hystograms reduction was made by the Kutcher and Burman's Effective Volume method. NTCP calculations by Lyman's models. The following variables were calculated: maximal dose for each organ (Dmax), Effective Volume (Veff), TD50 (Veff/Vref); NTCP for each organ of the patient; global UTCP for each patient. Differences between the 2 treatment techniques were analysed (2-field versus 4-field technique). For the NTCP calculations the computer application Albireo 1.0(R) was used.. 29 patients to assess with an average age of 54 +/- 10 years (range: 38-71); 65.5% men/34.5% women. The technique used was the field technique AP-PA in the 51.7% (15) and with 4 fields in 48.3% (14) of the cases. The global damage is estimated in 16% with a range between 0 and 37%. This goes up to 25% with the 2-field technique, with a wide range between 2 and 48% and it remains reduced to 4%, within a range between 0 and 12% when 4 fields are used. There were significant differences concerning the estimated damage probability (NTCP) on liver, spinal cord and left kidney, depending on the use of two or four fields.. NTCP and the global UTCP values of the organs at risk allow to compare a technique net benefit from another in each particular case, although in our theoretical study the comparison was done among the patients. It is important to stress that the calculations of the TCP and NTCP have a limited quantitative signification but they are useful and beneficial in order to decide between treatment plans when they are supported by the clinical knowledge.

Topics: Adenocarcinoma; Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Computer Simulation; Dose-Response Relationship, Radiation; Female; Fluorouracil; Gastrectomy; Humans; Imaging, Three-Dimensional; Kidney; Leucovorin; Liver; Male; Middle Aged; Organ Size; Organ Specificity; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Retrospective Studies; Risk; Spinal Cord; Stomach Neoplasms

The purpose of this study was to assess the efficacy and toxicity of intensity-modulated radiation therapy (IMRT) in the treatment of gastric cancer. Seven patients with gastric cancer were treated with IMRT. Six patients (all Stage III) received post-operative chemoradiotherapy with concurrent 5-fluorouracil and leucovorin. One received planned pre-operative radiation, though did not proceed to surgery. All patients were planned to receive 50.4 Gy in 1.8 Gy fractions. IMRT planning was compared with opposed anterior-posterior: posterior-anterior (AP/PA) and 3-field conventional three-dimensional plans. When compared with either AP/PA or 3-field plans, IMRT significantly reduced the volume exceeding the threshold dose of the liver and at least one kidney. Target coverage with IMRT was excellent, with 98+/-1% of the target receiving >or=100% of the dose. Compared with AP/PA and 3-field plans, IMRT plans had a greater percentage of target receiving the prescribed dose, but also a greater volume receiving >110% of the dose. IMRT was well tolerated; no patients developed acute gastrointestinal toxicity greater than grade 2. All seven experienced grade 2 nausea, three had grade 2 diarrhoea and two had grade 2 oesophagitis. Weight loss ranged from 0-12% (mean 6.1% and median 5.8%). IMRT in the treatment of gastric malignancies reduces the mean and above threshold doses to critical normal tissues. In an initial cohort of seven patients, 50.4 Gy delivered by IMRT is well tolerated and safe.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Middle Aged; Preoperative Care; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Treatment Outcome

Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is a need for newer regimens.. Twenty-five chemonaive patients with AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m(2) over 30 min on day 1 combined with leucovorin 200 mg/m(2) over 2 h followed by 5-fluorouracil 400 mg/m(2) as bolus and 600 mg/m(2) as a 22-hour infusion on day 1 and 2. The treatment was administered every 14th day until progression or intolerable toxicity.. Twenty-five patients (17 male, 8 female; 22 patients with PS 0-1 and 3 patients with PS 2), median age 54 (range 25-77), received a total of 230 courses of chemotherapy (median 9; range 1-18). Objective responses were observed in 9 patients (36%), all being partial. Median progression-free survival, 1- and 2-year progression-free survival rates were 8.6 months, 28.4% and 15.3%, respectively. Median overall survival, 1- and 2-year overall survival rates were 11.6 months, 48.0% and 17.8%, respectively. As serious adverse events, grade 3-4 neutropenia was observed in 5 patients (20.0%), grade 3 diarrhea in 4 patients (16.0%). No treatment-related death occurred.. FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate

Careful consideration must be given to the efficacy of treatment for elderly patients with advanced gastric cancer. Thirty-two elderly patients, 75 years of age or older with gastric cancer, were treated in Tokyo Metropolitan Komagome Hospital,Department of Chemotherapy, between January, 1993 to December, 2002. We analyzed the data of these patients retrospectively. The male/female ratio was 13:3, and 90.6% of the patients developed complications. Some 29 patients were treated with 5-FU regimen. The response rate was 17.2%, median survival time was 201 days, and 5 PR pts had 421 days' survival time. Patients with good PS had long survival times. A comparative study was conducted between 15 cases treated with cisplatin (CDDP) regimen and 14 cases without CDDP. Among them, 13 pts were given a low dose and 16 pts a full dose of chemotherapy (5-FU+/-CDDP). No differences were found between the two groups in overall survival time. No patients showed a severe adverse effect and some exhibited improvement by the chemotherapy. Therefore, the choice of chemotherapy for an elderly gastric cancer patient mostly depends on the patient' s general condition. Elderly patients can develop many complications, so the organ function test should be carefully evaluated. Development of an oral anticancer drug for gastric cancer is in progress and promises to show good results in the near future. Chemotherapy appears able to preserve good "Quality of Life" and will play an important role in the treatment of gastric cancer in elderly patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Hypertension; Leucovorin; Male; Methotrexate; Quality of Life; Retrospective Studies; Stomach Neoplasms; Survival Rate

Toxicities and their severities vary among advanced gastric cancer patients when they receive the same regimen containing continuous infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the key rate-limiting enzymes which is closely related to toxicities of 5-FU in chemotherapy. This study was to explore the relationship between activity of DPD and concentration of 5-FU, and their correlation to adverse events among advanced gastric cancer patients treated with the same regimen containing 5-FU continuous infusion.. Patients received the same regimen (intravenous injection of paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was collected from 36 patients with advanced gastric cancer before and after chemotherapy to detect the activity of DPD and concentration of 5-FU by high-performance liquid chromatography (HPLC). Adverse events were assessed every cycle.. Serum activity of DPD revealed a unimodel distribution, which globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD activity values were 2.38 and 2.13, respectively. No total DPD deficiency was found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1 589.2 microg/L, which demonstrated normality distribution after a logarithmic transformation was applied. The DPD activity was inversely correlated with 5-FU concentration (r=-0.376, P=0.024). The patients with low activity of DPD were more frequently suffering from severe diarrhea, mucositis, and myelosuppression. And high level of 5-FU concentration led to the increase of adverse events.. Pre-chemotherapy DPD activity and 5-FU concentration during chemotherapy vary among gastric cancer patients, which may help to prevent severe toxicities during the treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucositis; Neoplasm Staging; Paclitaxel; Stomach Neoplasms; Young Adult

To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer.. We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/leucovorin based chemotherapy.. Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test).. XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Codon; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Polymorphism, Genetic; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Stomach; Stomach Neoplasms; Treatment Outcome; Xeroderma Pigmentosum Group D Protein

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Lung Diseases, Interstitial; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Vitamin B Complex

Recently, a survival advantage has been shown using adjuvant chemoradiotherapy after complete resection of gastric cancer. If survival advantages are to be maintained, treatment-related complications must be minimised. In this study, we explored the dosimetric implications and toxicity of conventional large field gastric bed irradiation.. Between 2000 and 2002, 16 patients received adjuvant 5-fluorouracil (5-FU) chemoradiotherapy after complete resection of gastric cancer. Radiotherapy was simulator planned using anterior-posterior parallel opposed fields to 45 Gy in 25 daily fractions over 5 weeks.. Thirteen patients (81%) completed radiotherapy and eight patients (50%) completed chemotherapy as planned. Toxicity was the main factor for discontinuation. Substantial dose inhomogeneities were shown using retrospective computed tomography recreation of dose-volume histograms (DVHs) of the organs at risk.. Although the delivery of chemoradiotherapy using conventional two-dimensional simulator planning is a feasible technique, significant under-appreciation of dose inhomogeneity exists. Conformal computed tomography planning is vital to document doses received by organs at risk, especially the spinal cord and kidneys, which may receive high doses, and prospectively correlate these with acute and long-term toxicity in order to redefine organ at risk tolerances in the setting of chemoradiation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Radiometry; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

An 83-year-old man was admitted to our hospital for abdominal pain and severe vomiting. Gastrography and gastric endoscopy revealed that the pylorus was obstructed by a giant type 2 cancer in the lower gastric body. Furthermore, computed tomography revealed multiple metastases in the para-aortic lymph nodes. The man was unable to consume any food or liquid, and could not take medicine orally. Paclitaxel was not effective in treating the lymph node metastases or vomiting; therefore a chronomodulated schedule was used, which involved the administration of low doses of 5-fluorouracil, levofolinate calcium and cis-platinum (FLP) each night. After four cycles of low-dose FLP therapy, the patient was able to consume food orally. The patient has partially responded to this regime over five months. In the current study, low-dose FLP therapy with chronomodulation was considered an effective treatment, and there were no severe adverse side effects. This case suggested that low-dose FLP therapy with chronomodulation is promising for the treatment of gastric cancer in elderly patients who can not take medicine orally, and further trials are warranted.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Aorta; Chronotherapy; Cisplatin; Eating; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Stomach Neoplasms

Most results from clinical trials of neoadjuvant chemotherapy for gastric carcinoma are certain. Meanwhile, microsatellite instability (MSI) is thought to be a new mechanism of cell canceration. This study was to investigate the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma.. Two microsatellite loci D2S123 and D3S1298 in tumor samples from 48 patients with gastric carcinoma, received preoperative chemotherapy of 5-fluorouracil (5-FU) and leucovorin (CF), were analyzed by polymerase chain reaction (PCR), electrophoresis on 8% denatured polyacrylamide gel, and silver staining. The microsatellite statuses of preoperative and postoperative specimens were compared. Chi-square test was used to analyze the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma.. The detection rate of MSI was significantly higher in preoperative samples than in postoperative samples (31.3% vs. 12.5%, P=0.026). After neoadjuvant chemotherapy, 9 cases changed from MSI-positive to MSI-negative, while no MSI-negative cases became MSI-positive.. The neoadjuvant chemotherapy regimen of 5-FU/CF can induce some MSI-positive gastric carcinoma change to MSI-negative, but has no effect on MSI-negative cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; DNA, Neoplasm; Fluorouracil; Humans; Leucovorin; Microsatellite Instability; Microsatellite Repeats; Neoadjuvant Therapy; Stomach Neoplasms

A North American phase III trial has recently shown that postoperative chemoradiotherapy using the FUFOL Mayo Clinic regimen improves overall survival and relapse-free survival after surgical resection of gastric cancer. However, severe grade 3-4, hematologic and gastrointestinal toxicities were frequent. The aim of this retrospective and multicentric study was to determine the tolerance of a postoperative chemoradiotherapy regimen using LV5FU2 instead of the Mayo Clinic regimen.. Twenty-three patients with resected adenocarcinoma of the stomach or gastroesophageal junction at high risk of recurrence were treated with LV5FU2 chemotherapy and radiotherapy (45 Gy in 25 fractions and 5 weeks) delivered to the tumor bed and regional nodes. Nineteen patients were treated with two to four cycles before radiotherapy, then three cycles during radiotherapy, and finally four cycles after radiotherapy; four patients were only given three cycles during radiotherapy.. Of the 23 patients assigned to this protocol, 20 completed treatment (87%). There was only one interruption of treatment because of hematologic or gastrointestinal toxicity. Tolerance of LV5FU2 regimen associated with radiotherapy was excellent: one grade 3 or 4 gastrointestinal toxicity (4.3%), no toxic death, and only one grade 3 neutropenia (4.3%) were reported.. Radiotherapy combined with LV5FU2 appears to be better tolerated than the Mayo Clinic regimen used in the North American study. These results have to be considered when elaborating future postoperative chemoradiotherapy trials for gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Postoperative Care; Retrospective Studies; Stomach Neoplasms

Intergroup study 0116 (INT-0116) showed an 11% absolute improvement in 3-year survival with post-operative radiochemotherapy for gastric cancer, but reported 33% severe acute GI toxicity using conventional simulation with large fields. We adapted the treatment using conformal radiotherapy techniques and assessed toxicity and outcome in 20 consecutive patients.. A conformal radiotherapy technique previously developed for gastric lymphoma was adapted to treat the target volume defined in INT-0116. The five-field plan used a large anterior field, plus asymmetrically matched upper AP:PA fields and lower lateral fields. Consecutive patients with ECOG PS 0-2 and stage IB-IV non-metastatic gastric cancer were treated with 5-FU (425 mg/m2 daily x 5 days) and leucovorin (20 mg/m2 daily x 5 days) for one cycle prior to and two cycles following concurrent radiation (45 Gy/25 fractions) with identical drug dosages on the first 4 and last 3 days of radiation. Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria. Patient charts were reviewed in November 2003 and late toxicity and outcome were recorded.. Nineteen of 20 patients completed radiotherapy and 14 completed all chemotherapy cycles. One patient died of neutropenic sepsis. Maximum acute toxicity [grade (number)] was: 5(1), 4(0), 3(4), 2(10), 1(4), 0(1). There were two grade 1 late toxicities. Two-year overall survival is 70% (95% confidence interval: 50-90).. Conformal radiotherapy may improve acute toxicity (25% grade 3 or greater toxicity as compared with 41% reported in INT-0116). Survival is comparable to that achieved in the INT-0116 treatment arm (approximately 60% at 2 years). INT-0116 results can be achieved outside a study setting; however, further efforts to improve treatment efficacy and minimize toxicity are warranted.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Outcome Assessment, Health Care; Radiotherapy, Conformal; Stomach Neoplasms; Survival Analysis

The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer.. From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy.. The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160).. Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Adjuvant; Stomach Neoplasms; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Digestive System Surgical Procedures; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Radiography; Remission Induction; Retroperitoneal Neoplasms; Stomach Neoplasms; Taxoids; Treatment Outcome

We describe our experience with a patient who had undifferentiated gastric carcinoma with extensive lymph node metastasis, including para-aortic lymph-node metastasis, and had a complete response to induction therapy with methotrexate plus 5-fluorouracil (sequential therapy with MTX, 5-FU, and Leucovorin) and secondary treatment with oral TS-1. The patient was a 71-year-old woman with a massive gastric tumor (signet ring cell carcinoma), occupying most of the stomach. A computed tomographic (CT) scan revealed para-aortic, celiac, and common hepatic lymph-node metastases. Stage IV disease was diagnosed. Palliative total gastrectomy was performed to control bleeding and to improve oral intake of food. Two courses of induction therapy with MTX, 5-FU, and Leucovorin were started 3 weeks after surgery. A CT scan revealed residual lymph node metastasis. The response was assessed to be no change, but the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 improved from 7,028 ng/ml and 726 U/ml 3 weeks after surgery to 2,832 ng/ml and 281 U/ml, respectively. Secondary treatment with oral TS-1 was begun, and a CT scan showed distinct shrinkage of lymph-node metastases. There was no serious toxicity. The levels of CEA and CA19-9 decreased markedly to 2.9 ng/ml and 16 U/ml, respectively, about 6 months after surgery and remained at 3.7 ng/ml and 16 U/ml, respectively, about 1 year after surgery.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Methotrexate; Oxonic Acid; Palliative Care; Pyridines; Stomach Neoplasms; Tegafur

The role of second-line chemotherapy in gastric cancer is not yet established. We analyzed patients receiving second-line treatment after chemotherapy with cisplatin, infusional 5-fluorouracil, folinic acid (PLF).. 27 patients took part in this retrospective analysis. The second-line chemotherapy consisted of different regimens depending on the recommendations of the attending physician based on response to and toxicity of first-line treatment.. In 3 of 27 patients, partial response was achieved (11%, 95%-confidence interval 0-23%). The progression-free survival and overall survival was 3.1 (2.1-4.3) and 5.1 (3.8-6.6) months, respectively. Progression-free intervals (PFI) of more than 7 months after first-line therapy were a predictor for patients who may benefit from the treatment (median survival from the start of second-line therapy: 10.6 (6.6-13.1) months).. Second-line chemotherapy after cisplatin / 5-FU rarely induced tumor response, and progression-free survival as well as overall survival remained short. Based on our data, we hypothesize that the PFI after first-line treatment may be a selection criterion for patients suitable for second-line chemotherapy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Female; Fluorouracil; Germany; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Salvage Therapy; Stomach Neoplasms; Survival Rate; Treatment Failure; Treatment Outcome

The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety.. Twenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles.. Twenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2.. Chronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronotherapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Docetaxel; Doxorubicin; Drug Combinations; Etoposide; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Methotrexate; Organoplatinum Compounds; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5-FU treatment.. Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled. P maximum (P max), P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration) were measured from the 12-lead ECG at the 0th and 48th hour of the first chemotherapy cycle. Echocardiography was also obtained in all patients at the same times.. Clinical cardiotoxicity was observed in two patients. P max and Pd were both significantly longer after 5-FU treatment at the 48th hour (P < 0.001). P min did not change (P > 0.05).. Treatment with 5-FU based regimens may increase Pd and prolong the P max in cancer patients. These alterations may be predictive of patients at risk of atrial arrhythmias during 5-FU treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Carcinoma; Colorectal Neoplasms; Coronary Artery Disease; Coronary Vasospasm; Coronary Vessels; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography; Electrocardiography; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Stomach Neoplasms; Time Factors

The patient is a 66-year-old male who underwent gastrojejunostomy at another hospital with the diagnosis of type 3 unresectable gastric cancer. He was admitted to our hospital for adjuvant chemotherapy. A CT scan revealed both peritoneal dissemination and a large tumor directly invading the pancreas and liver. After 7 courses of combined chemotherapy with 5-FU, Leucovorin, cis-platinum and methotrexate, an effective response, tumor reduction and the disappearance of peritoneal dissemination, was verified by CT scan. Pancreatoduodenectomy with transverse colectomy was carried out and the pathological diagnosis was also curative (pT3, pN1, pP0, HO: stage III A). Although he unfortunately died from peritoneal recurrence after 9 months, he maintained good quality of life after re-operation. We think this case shows the possibility of NAC for patients with far advanced gastric cancer with peritoneal dissemination to improve their prognosis or QOL.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Jejunostomy; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Neoadjuvant Therapy; Neoplasm Invasiveness; Pancreatic Neoplasms; Peritoneal Neoplasms; Quality of Life; Stomach Neoplasms

Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Calcium Carbonate; Catheterization, Central Venous; Catheters, Indwelling; Chemical Precipitation; Colorectal Neoplasms; Crystallization; Device Removal; Equipment Failure Analysis; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Palliative Care; Pancreatic Neoplasms; Stomach Neoplasms; Surface Properties

The combination of 5-fluorouracil (5-FU) modulated by folinic acid (FA) and cisplatin is commonly used in advanced digestive non-colon cancers (ADNCC). In order to simplify treatment administration by avoiding cisplatin-related hydration, we investigated a weekly regimen of 5-FU/FA/cisplatin. Patients with ADNCC were treated with 5-FU 2.0 g/m2, FA 500 mg/m2 and cisplatin 25 mg/m2 day 1, for 6 weeks with a 2-week rest, and were assessed for toxicity, tumor response and disease-free survival. Forty-three patients with measurable ADNCC were treated with this weekly regimen. Primary tumor sites were mainly esophagus (n = 17), stomach (n = 12) and pancreas (n = 9). Results were as follows. Toxicity was mostly hematological, with 16% grade 3/4 neutropenia (seven of 43) and 4% febrile neutropenia (two of 43). Objective response (OR) was observed in 19 of 43 (44%) patients including four complete responses (9%) and 15 partial responses (35%). Another 18 patients (42%) experienced stable disease. Time to progression was 6.5 months. The median response and stable disease durations were 4.3 (range 3-34) and 5 (range 2-16) months, respectively. We conclude that weekly administration of 5-FU/FA/cisplatin is an active and well-tolerated regimen. Toxicity is manageable and allows chemotherapy on an outpatient basis without hydration program as required when cisplatin is used at the dose of 50 mg/m2.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cisplatin; Digestive System Neoplasms; Disease Progression; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Pancreatic Neoplasms; Stomach Neoplasms

This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer.. Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test.. Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor.. FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging.

Topics: Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Disease-Free Survival; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

We performed radio-frequency ablation (RFA) therapy combined with intra-arterial chemotherapy for a 71-year old female gastric cancer patient with liver metastasis. She underwent total gastrectomy due to advanced gastric cancer in July of 1996. Because CT scans revealed multiple liver tumors with her, she also underwent intra-arterial chemotherapy comprising of 5-fluorouracil, cis-platinum and Leucovorin. Although her liver tumors decreased in size and number, after 9 months, we had to remove the catheter because of hepatic artery obstruction. Immediately after the removal, 5 hepatic metastases appeared, which were 3.5 cm in maximum diameter. After RFA therapy, CT scans revealed homogenously attenuated lesions. Liver biopsy demonstrated a complete coagulation necrosis. She is currently alive going into 19 months after liver metastasis and 7 months after RFA.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Catheter Ablation; Cisplatin; Female; Fluorouracil; Gastrectomy; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Stomach Neoplasms

Gastric cancer has the highest incidence rate and mortality rate among gastrointestinal malignancies. Twenty percent of the patients with dissectable gastric cancer cannot be cured simply by surgery due to local infiltration and distant metastasis. To evaluate the therapeutic effectiveness and safety of oxaliplatin combined with 5-fluorouracil and leucovorin on the patients with gastric carcinoma after palliative gastric resection, we analyzed all of the cases of gastric adenocarcinoma undergone palliative gastric resection in our Cancer Center in recent years.. A total of 41 patients who underwent palliative gastric resection from Jan. 2000 to May 2004 in our Cancer Center were evaluated. Chemotherapy was given 8-18 days post-surgically with oxaliplatin (130 mg/m(2), intravenus infusion) on day 1, leukovorin (200 mg/m(2)) on day 1, 5-FU (500 mg/m(2), infusion) on day 1 followed by (5-FU 2600 mg/m(2), continuous infusion) for 48 h, the cycle was repeated every 4 weeks. Primary evaluation was performed after 3 cycles of chemotherapy. The chemotherapy was terminated in the patients without response to the treatment. In the patients with response to the treatment, the chemotherapy continued until 6-8 cycles for further analyses.. None of the patients died from surgery or chemotherapy. Complete response occurred in 2 cases, partial response occurred in 19 cases, stable disease in 8 cases, and progressive disease in 12 cases. The total response rate was 52.5%. The 1-year, 2-year, and 3-year survival rates were 71%, 43%, and 32%, respectively. The side effects included neuropathy, nausea, vomiting, and myelosuppression. No grade 3 or 4 myelosuppression was observed.. Palliative surgery in late stage gastric cancer followed by combination chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin is a safe therapeutic modality with promising short-term effectiveness and mild side effects.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Remission Induction; Stomach Neoplasms; Survival Rate

Clinical study showed that paclitaxel (PTX) may be used to treat gastric cancer. The combination of PTX and 5-fluorouracil (5-FU) is effective, and safe in treating advanced gastric cancer. This study was to investigate efficacy of biweekly regimen of high dose of leucovorin (CF), 5-FU, and PTX on advanced gastric cancer, and its toxicities.. Twenty patients with advanced gastric cancer received biweekly regimen of CF/5-FU/PTX (200 mg/m(2) of CF, intravenous infusion for 2 h, day 1; 500 mg/m(2) of 5-FU, intravenous injection, day 1; 1 500 mg/m(2) of 5-FU, intravenous infusion for 46 h, day 1, 2; 90 mg/m(2) of PTX, intravenous infusion for 3 h,day 1). Efficacy, and toxicities were evaluated after 4 cycles.. Total response rate was 65.0% (13/20) with 2 (10.0%) cases of complete remission (CR), and 11 (55.0%) cases of partial remission (PR). No treatment- related death occurred. Stomatitis, hand-foot syndrome, and loss of hair were main toxicities.. Biweekly regimen of high dose of CF, 5-FU, and PTX may achieve a high response rate with tolerable toxicities in patients with advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Paclitaxel; Remission Induction; Stomach Neoplasms; Stomatitis

This retrospective study aimed to ascertain the expression of erbB2 in relation to topoisomerase II alpha (T2 alpha) and thymidylate synthase (TS) markers in 30 consecutive metastatic gastric cancer patients with a specimen available for study.. All patients had been entered on consecutive chemotherapeutic clinical trials that were all 5-fluorouracil based. The specimens were evaluated by fluorescence in situ hybridization to ascertain erbB2 and T2 alpha gene amplification, and by immunohistochemical staining for T2 alpha and TS protein expression.. erbB2 amplification was detected in 16.7% of specimens, with co-amplification of the T2 alpha gene in 40%, and 44% had undetectable TS protein expression. Kaplan-Meier survival curves showed significantly prolonged overall survival in patients with erbB2 and T2 alpha gene amplification, T2 alpha protein overexpression and absence of TS protein expression (P = 0.0011, P = 0.0048, P = 0.0061 and P = 0.0267, respectively, by log rank test). There was a positive correlation between erbB2 amplification and T2 alpha amplification, T2 alpha protein overexpression, and a trend towards absence of TS expression (P = 0.0001, P = 0.003 and P = 0.066 by Fisher's exact test).. High dose fluorouracil/leucovorin-based chemotherapy may have the potential to reverse the adverse effects resulting from erbB2 gene amplification in gastric cancer.

Topics: Adult; Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; DNA Topoisomerases, Type II; DNA-Binding Proteins; Female; Fluorouracil; Gene Amplification; Humans; In Situ Hybridization, Fluorescence; Leucovorin; Liver Neoplasms; Male; Middle Aged; Prognosis; Receptor, ErbB-2; Retroperitoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Thymidylate Synthase

To observe the influence of chemotherapy on the switching of Th1/Th2 cytokines in stomach cancer patients.. Th1/Th2 cytokine genes expressed by peripheral blood mononuclear cells of stomach cancer patients before and after chemotherapy were detected by RT-PCR.. The expression of Th2 cytokines was dominant in patients before chemotherapy, and the dominancy became less marked after chemotherapy.. The immune deviation with Th2 predominance in stomach cancer patients has a tendency to become reversed after chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Interferon-gamma; Interleukins; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Th1 Cells; Th2 Cells

A 68-year-old male with a history of gastric resection for gastric cancer underwent resection of the sigmoid colon for a sigmoid colon cancer in February, 2000. The cancer was classified as stage III b. After operation, l-LV + 5-FU therapy was administered, but metastases to the abdominal wall, right inguinal lymph node and spleen developed in succession, and resection was repeated. In October 2001, 1 year and 8 months after sigmoidectomy, however, multiple metastasis to the intraperitoneal lymph node had developed. As surgery was not indicated, TS-1/CDDP combined chemotherapy was started. TS-1 80 mg/day was administered for 4 weeks, the drug was withdrawn for 2 weeks and CDDP 80 mg was injected by intravenous drip at the 8th day of TS-1 administration, which was used as one course. From the second course after inception of the administration, CA19-9 decreased, and after the third course the upper intraperitoneal metastatic lesion disappeared on CT. CR has been continued for 4 months up to the present. Our results suggest a possibility that this therapy is effective not only for gastric cancer but also for colon cancer. This therapy can be administered at home. It is considered to be a useful therapy from the viewpoint of QOL as well. The high DPD activity of the tumor may have been one reason this treatment was effective. This case also seems significant from the viewpoint of attaining individualization of the drug selection in chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colon, Sigmoid; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Infusions, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Sigmoid Neoplasms; Splenic Neoplasms; Stomach Neoplasms; Tegafur

This study was performed to determine the prognostic factors of 102 nonresectable locally advanced or metastatic gastric cancer patients prospectively treated with a multimodulation of 5-fluorouracil (5FU), hydroxyurea, leucovorin, and cisplatin. Response rate in 85 patients with measurable disease was 62.4% (95% confidence interval 51.9% to 72.9%). A weight increase (5% or more) was observed in 47% of patients, performance status improved in 70.6%, and symptoms disappeared in 69%. Median times for progression-free survival and overall survival were eight and 11 months, respectively. Liver metastases, more than two involved sites, and increased carcinoembryonic antigen (CEA) were found to be univariate adverse prognostic factors for survival. In a multivariate analysis, only the presence of liver metastasis was found to be an independent prognostic factor. Response rate and survival in patients with gastric linitis or diffuse forms were in the same range as in patients with intestinal forms of gastric adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Cisplatin; Disease-Free Survival; Drug Evaluation; Female; Fluorouracil; Gastrointestinal Diseases; Hematologic Diseases; Humans; Hydroxyurea; Karnofsky Performance Status; Kidney Diseases; Leucovorin; Life Tables; Liver Neoplasms; Male; Middle Aged; Nervous System Diseases; Prognosis; Proportional Hazards Models; Quality of Life; Risk Factors; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Weight Gain

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil UFT], tegafur + gimeracil + osteracil [S-1 (TS-1)]) relative to DPD activity, with other fluoropyrimidines as controls.. The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancer patients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients.. In patients with low DPD activity (under 40 U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40 U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (16), and progressive disease (PD) in the rest. UFF induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6).. It is recommended to use S-1 rather than UFF in patients with high DPD activity. Measurement of DPD was useful in drug selection.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Dihydrouracil Dehydrogenase (NADP); Disease Progression; Drug Combinations; Enzyme Inhibitors; Fluorouracil; Humans; Japan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Oxidoreductases; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Pyridines; Statistics as Topic; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

To evaluate the effects and safety of OXA-LV5FU2 regimen for patients with advanced/metastatic gastric cancer.. OXA 100 mg/m(2) i.v. 2hr d1, LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600 mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was evaluated at 4 cycles (8 weeks).. Forty three patients have been entered into the study. Patients with primary tumor resected or non-resected were 17 and 26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12 liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty patients were evaluable for clinical response. Four patients achieved CR (10.0%), 13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%). Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median time to progress (mTTP) was 5 months and median overall survival (mOS) was 8 months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral neuropathy toxicity or any deaths during treatment.. OXA-LV5FU2 is a high response regimen for advanced gastric cancer with mild toxicity, which can be practiced safely.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms

Gastric adenocarcinoma is a high-lethality tumour and has a great tendency to recur. Liver and peritoneum are the places where the metastases are most frequently localised. We introduce the case of a woman diagnosed with gastric adenocarcinoma who showed isolated skin metastasis. There were an important number of recurrences (always in the skin). She was treated with radical surgery and later treated with different cytostatic schedules. The patient died 13 years after metastasis were diagnosed. With this case we wanted to pay attention to the role of the biologic prognostic factors of gastric carcinoma. The molecular biology of these tumours can explain the different evolution of the disease. Biologic prognostic factors can separate gastric carcinoma into different kinds of disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Cobalt Radioisotopes; Combined Modality Therapy; Etoposide; Fatal Outcome; Female; Fluorouracil; Gastroenterostomy; Humans; Leucovorin; Middle Aged; Radioisotope Teletherapy; Shoulder; Skin Neoplasms; Stomach Neoplasms; Stomach Ulcer; Survivors

To evaluate the therapeutic effects of hydroxycamptothecin (H) combined with leucovorin (L), fluorouracil (F) and cisplatin (P) on advanced cancer of gastric cardia and colorectal cancer.. Sixty-five patients with advanced cancer of gastric cardia or colorectal cancer were treated by LFH or LFPH regimen. All patients completed four cycles of treatment, in 21 days per cycle.. The overall response rate (RR) was 26.2% (17/65) with partial response (PR) in 17 patients, stable disease (SD) in 31 and progressive disease (PD) in 17. The clinical benefit response rate (CR + PR + SD) was 73.8% (48/65). The RR were 32.3% (10/31) for untreated patients and 20.6% (7/34) for retreated patients. The stable rate was 47.7% (31/65). The RR of patients with cancer of gastric cardia were 33.3% (5/15) for untreated treatment and 29.4% (5/17) for retreated ones. Median survival time (MST) was 10 months. Median time to progression (MTTP) was 8 months. Grade 3 - 4 toxicities were stomatitis (10.8%), nausea and vomiting (12.3%) and leukopenia (6.2%). Most patients (> 80%) developed Grade 1 - 2 alopecia.. The regimen of HCPT combined with LV, 5-Fu and DDP appears to be an effective and tolerable therapeutic option for advanced cancer of gastric cardia and colorectal cancer, especially for the former and retreated patients, giving a satisfactory stable rate though not very high.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cardia; Cisplatin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Biopsy; Combined Modality Therapy; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Male; Prognosis; Pyloric Antrum; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Stomach Neoplasms; Time Factors

Phase II clinical trails showed that paclitaxel is effective in treatment of advanced gastric cancer (AGC). The combination of paclitaxel and 5-fluorouracil (5-FU) in the treatment of advanced gastric cancer is effective and safe. This study was designed to evaluate the efficacy and the toxicity of paclitaxel combined with semimonthly 5-FU/Leucovorin for the AGC patients.. Twenty-five measurable patients with AGC proved pathologically were enrolled into this study. The chemotherapy regimen was comprised of paclitaxel,75 mg/m(2) i.v. in a 3-hour infusion followed by 2-hour infusion of leucovorin 200 mg/m(2), then 10-minute intravenous bolus of 5-FU 375 mg/m(2), then 48-hour infusion of 5-FU 2.8 g/m(2) using an ambulatory pump. The regimen was given per 14 days. One cycle consisted of twice chemotherapy regimens. All enrolled patients received at least two cycles of treatment.. After two cycles of chemotherapy, the complete remission and the partial remission were 8% and 60%, respectively. The median duration of response was 4 months. No treatment-related death occurred. Phlebitis,feeling disorder, and alopecia were main side effects.. Semimonthly 5-FU/LV combined with paclitaxel has high release rate but comparatively mild toxicity for AGC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Paclitaxel; Stomach Neoplasms

We have reported a 33% response rate with 5-fluorouracil/leucovorin (5-FU/LV) treatment along with a median survival of 7 months in patients with advanced gastric cancer. Subsequently, mitomycin C (MMC) became our target agent for the combination because of its activity towards gastric cancer.. From May 1998 to December 2000, a total of 37 chemo-naive patients with advanced gastric cancer were included. There were 20 men and 17 women with a median age of 58 (range, 21-73) years. The regimen consisted of 2600 mg/m2 5-FU and 100 mg/m2 LV admixed in an outpatient infusion pump administered for 24 hours every week for 6 weeks, followed by a 2-week break; then 10 mg/m2 MMC was given once every 8 weeks. The treatment continued until disease progression or unacceptable toxicity was noted, or the patient refused.. In total, 404 treatments of 5-FU/LV were given. The mean number of treatments was 10 (range, 1 to 24). The intent to treat response rate was 40.5% (15/37) with 5.4% (2/37) showing a complete response. The median time to disease progression was 4.5 months. The median survival time was 8.0 months. All of the patients were evaluated for toxicity. Less than 10% of the patients developed grade III/IV toxicity.. MMC with weekly 24-hour infusions of high-dose 5-FU and LV produced moderate activity in patients with advanced gastric cancer, and patients showed acceptable toxicity.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Stomach Neoplasms; Survival Rate; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate

We report a case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP, docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric cancer and metastatic lymph nodes were remarkably reduced and the effect of this therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3), which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the first-line chemotherapy for metastatic advanced gastric cancer in Japan; however, a second-line chemotherapy has not been established. As in this case, a TXT based regimen is effective and well tolerated therapy as a second-line chemotherapy for metastatic gastric cancer after prior exposure to CDDP and 5-FU.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Resistance, Neoplasm; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Stomach Neoplasms; Taxoids

Afferent loop syndrome (ALS) is a debilitating complication of recurrent gastric cancer. Surgical intervention is usually not feasible in the face of poor general performance, presence of advanced peritoneal carcinomatosis and limited survival of the patients. Non-surgical approaches include internal drainage by stenting at the stenotic or anastomotic site and external drainage via the percutaneous routes. Percutaneous transhepatic duodenal drainage (PTDD) has been shown to provide effective palliation for ALS, but long-term catheterization is usually inevitable. We hereby present two cases of recurrent gastric cancer whose ALS was successfully treated with PTDD followed by weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin (HDFL). PTDD rapidly ameliorated the incapacitating symptoms of ALS, and the effective, low-toxicity chemotherapy subsequently led to tumor regression, restoration of bowel patency and removal of the drainage tube. At present, both patients have remained ALS-free and drainage-free for 16 and 17 months, respectively. Our results indicate that this non-surgical approach with PTDD followed by weekly HDFL could serve as a safe and effective treatment for ALS in recurrent gastric cancer complicated by peritoneal carcinomatosis.

Topics: Adenocarcinoma; Afferent Loop Syndrome; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Dose-Response Relationship, Drug; Drainage; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Palliative Care; Peritoneal Diseases; Peritoneal Neoplasms; Stomach Neoplasms; Treatment Outcome

The prognosis for gastric cancer patients who undergo noncurative resection is extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for primary noncurative gastric cancer. Thirty-four patients with biopsy-proven noncurative gastric cancer were treated with either of two neoadjuvant chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C). Noncurability was determined by conventional staging procedures, staging laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of the tumors was reassessed. Patients who were judged to be candidates for curative resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a major response [0 complete response (CR), 8 partial response (PR)]. In three patients the second laparoscopy revealed disappearance of the peritoneal metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8 curative resections (2 curability A, 6 curability B). Pathologic examinations revealed a grade 2 response in eight patients but no grade 3 response. Univariate analysis showed the following to be significant prognostic factors: histology type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no change vs. progressive disease; p = 0.002), and salvage surgery (resected vs. unresected; p = 0.001). Among these factors, salvage surgery was found to be the only independent prognostic factor by multivariate analysis, with a relative risk of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%), gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for primary noncurative gastric cancer when salvage surgery can be performed. A chemotherapy regimen with a higher complete response rate would improve the prognosis of this dismal disease even more.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Mitomycin; Neoplasm Staging; Preoperative Care; Prognosis; Salvage Therapy; Stomach Neoplasms; Survival Analysis

Today, no effective chemotherapy regimen has been established for non-resectable or postoperative recurrent gastric cancer, and most such therapy seems to be palliative. Thus, a highly effective chemotherapy that allows good patient QOL is desired. We report three gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, CPT-11. The treatment protocol was tegafur 1,200 mg/body, days 1-12 (continuing 16 h, intravenously with 800 mg/body from 16 to 24 h, 400 mg/body from 24-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, 8-12, (16 h, one shot infusion), Isovorin 25 mg/body, days 1-5, 8-12 (16 h, one shot infusion), followed by CPT-11 100 mg/body, days 13 (one shot infusion). We performed 1 or 2 courses, and with 2 courses the CPT-11 dose was increased to 150 mg/body. The first patient was a 54-year-old female with advanced type 3 gastric cancer with liver metastasis (H3). After chemotherapy (2 courses), there was a 30% reduction in the advanced gastric cancer and a 95% reduction in the liver metastasis. The second patient was a 73-year-old male with recurrent type 1 gastric cancer in the remnant stomach 24 months after partial gastrectomy. After chemotherapy (1 course), there was a 45% reduction in advanced gastric recurrent cancer. The third patient was a 67-year-old male with advanced type 2 plus 3 gastric cancers with liver (H3) and abdominal lymph node metastases. After chemotherapy (1 course), there was a 70% reduction in the type 2 and 55% reduction in the type 3 advanced gastric cancer, and a 50% reduction in the liver metastasis and 35% reduction in the abdominal lymph node metastasis. The only adverse effect was grade 2 pancytopenia, gastrointestinal disorder, and alopecia. In conclusion, this regimen resulted in good intrachemotherapeutic QOL and was highly effective in advanced gastric cancer patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chronotherapy; Cisplatin; Female; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Tegafur

We report a case in which weekly paclitaxel (TXL) administration was effective for gastric cancer with malignant ascites. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. The patient was a 49-year-old woman who suffered from non-resectable gastric cancer, staged intraoperatively as having severe lymph node metastasis and malignant ascites. As an outpatient treatment, she was first treated with 5-fluorouracil combined with high-dose Leucovorin for 4 cycles. However, she complained of abdominal fullness and ascites, and received weekly TXL administration as the second line treatment. The ascites had completely disappeared 3 months after administration. The toxic events were anemia (grade 1) and alopecia (grade 2). No major adverse effects such as hypersensitivity reaction, leukopenia or peripheral neuropathy were observed.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Paclitaxel; Stomach Neoplasms; Treatment Outcome

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Gastrectomy; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Stomach Neoplasms

The patient was a 65-year-old woman with type 3 gastric cancer (por) in the upper third of the stomach invading esophagus. Because of No. 16 lymph node swelling on abdominal CT examination, she was treated with FLP (5-fluorouracil + Leucovorin + cisplatin) as a neoadjuvant chemotherapy (NAC). The activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in the primary tumors upon endoscopic examination were 2.72 pmol/g tissue and 129.1 pmol/mg/min, respectively. After the second course, we carried out lower esophagectomy and spleno-total gastrectomy with D3 including the No. 16 lymph nodes. Histopathological examination of resected specimens showed dense fibrosis and xanthogranulomatous inflammation with foamy cells and giant cells. No residual carcinoma was seen (complete response). The patient is still alive with no sign of recurrence 1 year after surgery. NAC by combination of FLP is thought to be effective for the treatment of highly advanced gastric cancer, especially in cases with locally advanced disease and lymph node metastasis such as the present. Although no relations were seen between NAC effects and TS, DPD activities and TSIR in primary tumors in 12 gastric cancer patients, the survival rate of a low DPD activity group was significantly better than a high group in 106 cases undergoing adjuvant chemotherapy including 5-FU after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dihydrouracil Dehydrogenase (NADP); Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxidoreductases; Remission Induction; Stomach Neoplasms; Thymidylate Synthase

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Combined Modality Therapy; Fluorouracil; Gastrectomy; Humans; Leucovorin; Multicenter Studies as Topic; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate

A 68-year-old woman was admitted to our hospital because of type 4 gastric cancer associated with paraaortic lymph node metastasis. Considered surgically incurable, she was placed on preoperative chemotherapy consisting of Methotrexate (MTX) 50 mg (day 1), CDDP 10 mg (day 2-6), 5-FU 500 mg (day 1-6) and Leucovorin (LV) 60 mg (day 2-6). Because of severe nausea and leucopenia, she could receive only 1 course of the chemotherapy. CT on January 7, 1997 (5 weeks after the chemotherapy) showed that the gastric wall thickness and the paraaortic lymph nodes swelling had decreased remarkably. She underwent total gastrectomy on January 13, 1997 (pT2, pN2, pM1 (LYM), stage IV, TNM classification). As an outpatient, she was treated with UFT-E 300 mg/day (continuous until the present) and MTX 50 mg (day 1), 5-FU 500 mg (day 1) and LV 60 mg (day 2-3) once two weeks (total 27 cycles). Four years and 4 months after surgery, although peritoneal recurrence was suspected, she has been managed at our outpatient clinic.

Topics: Adenocarcinoma, Scirrhous; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Methotrexate; Stomach Neoplasms; Survivors; Tegafur; Uracil

A 63-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastasis of the liver. He was treated with 300 mg/day of UFT-E from 18 days after total gastrectomy on July 14, 1997. The preoperative serum level of tumor marker, which had been increasing (CEA: 340 ng/ml, CA19-9: 9,094 U/ml), returned to the normal range 7 months after gastrectomy. CT scan on July 9, 1998 (1 year after gastrectomy) showed that the liver metastasis had changed to a scar (CR). As of May, 2001, 2 years and 10 months after inducing CR, we have been administering UFT-E to the patient, with no side effect or regrowth of the tumor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Leucovorin; Liver Neoplasms; Lymph Node Excision; Male; Methotrexate; Middle Aged; Remission Induction; Stomach Neoplasms; Tegafur; Uracil

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Prognosis; Severity of Illness Index; Stomach Neoplasms; Treatment Outcome

The patient was a 67-year-old man who had undergone distal gastrectomy because of early gastric cancer without lymph node metastasis two years earlier. The postoperative course was uneventful, but he was admitted again to our hospital because of abrupt jaundice. A CT scan of the abdomen showed obstructive jaundice due to the enlargement of the lymph nodes around the hepatoduodenal ligament, pancreas head, portal vein, and celiac axis. After percutaneous transhepatic cholangio-drainage (PTCD), 5 cycles of FLP combination therapy (5-fluorouracil, leucovorin, cisplatin) were performed. Consequently, the tumor marker level returned to the normal range and the shrinkage of the metastatic lymph nodes was remarkable. A reopening of the biliary tract was attained, so the PTCD tube could be removed. As an outpatient without recurrence he has received oral administration of uracil plus tegafur. The FLP combination therapy was effective for obstructive jaundice due to intraperitoneal lymph node recurrence of the gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholestasis; Cisplatin; Drainage; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Recurrence; Stomach Neoplasms

A 56-year-old male was admitted for treatment of advanced gastric cancer. The patient was diagnosed as having an unresectable advanced gastric cancer because cancer cells had invaded the pancreas head and there were metastatic lymph nodes. The patient underwent preoperative chemotherapy (FLEP: intra-arterial infusion of CDDP, ETP and intravenous infusion of 5-FU, LV). The primary tumor and metastatic lymph nodes were reduced by three course of chemotherapy. The patient underwent curative resection and survived without recurrence for 14 months after operation. Preoperative chemotherapy using FLEP was performed in 15 patients with unresectable primary advanced gastric cancer. This therapy resulted in significantly higher survival times. In conclusion, FLEP has been shown to be effective for unresectable advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Etoposide; Fluorouracil; Gastrectomy; Humans; Infusion Pumps, Implantable; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Preoperative Care; Stomach Neoplasms

Recently, as society ages there have become more elderly gastric cancer patients with/without several complications(cerebrovascular diseases, cardiac diseases, atherosclerosis, DM, etc.), that were non-resected and require highly effective chemotherapy and good QOL. We report two elderly gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, S-1. The treatment protocol was tegafur 800 mg/body, days 1-7 (continuing 16 h, intravenously with 500 mg/body from 16 to 0 h, 300 mg/body from 0-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, (16 h), Isovorin 25 mg/body, days 1-5, (16 h, oneshot infusion, for 4 courses followed by a week rest. Next was S-1 120 mg/body x 2 times orally for 28 days, followed by 2 weeks rest, the administered for another 28 days. The first patient was 74 years of age, with advanced type 3 plus early type IIc gastric cancers with liver metastasis (H1). After chemotherapy the liver metastasis disappeared, there was a 70% reduction in the advanced cancer and the early cancer disappeared. The second patient was 84 years of age, with advanced type 3 gastric cancer invading the esophagus. After chemotherapy, the primary lesion was reduced 80% and the esophageal invasion mass shrunk. The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chronotherapy; Circadian Rhythm; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Leucovorin; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A case featuring very late and unusual metastasis of gastric cancer is presented. A 49-year-old woman presented with metastatic disease in the seventh cervical vertebra 9 years after a total gastrectomy for gastric carcinoma. The resected primary tumor was a Borrman type III, poorly differentiated adenocarcinoma which had invaded the subserosal layer of the stomach and had generated lymph node metastases. The patient was treated for the metastatic tumor with sequential administration of cisplatin, calcium leucovorin and 5-fluorouracil and subsequent irradiation. Remission was achieved and she survived for a further 13 months without major symptoms.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Stomach Neoplasms

A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Methotrexate; Middle Aged; Stomach Neoplasms

The paper reports the data on treatment of 57 patients with disseminated gastric and colorectal carcinoma using a combination of mutamycin + 5-fluorouracil + leucovorin + cisplatin. Overall response was 26.3% including complete--7.01 and partial--19.29%. Mean duration of complete and partial remission was 10.88 +/- 5.65 and 5.18 +/- 0.82 months, respectively. Treatment as first-line chemotherapy was significantly more effective (36.1 and 9.5%). The regimens proved relatively low-toxic and therefore, can be recommended for out-patient application.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Neoplasm Recurrence, Local; Outpatients; Stomach Neoplasms; Time Factors

We describe a case of an acute myelogenous leukemia (AML) associated with t(1;11) (q23;p15), which is a novel simple variant translocation of t(7;11)(p15;p15). The patient was a Japanese man who had a history of non-Hodgkin lymphoma (NHL) and received MACOP-B combination chemotherapy. Fifteen months after the completion of the treatment, the patient developed AML (M2), which was regarded as a therapy-related leukemia. Cytogenetic study of bone marrow cells showed t(1;11). Although he achieved complete remission by combination chemotherapy, a relapse of NHL and gastric cancer were revealed in the course of the consolidation chemotherapy for AML. The NHL was considered a histological conversion from follicular lymphoma because lymphoma cells carried t(14;18) (q32;q21) and were strongly positive for BCL2 protein. Translocation (1;11), together with AML having t(7;11) or inv(11) involving 11p15, shows that 11p15 is a common acceptor site of these chromosome aberrations and suggests the significance of the NUP98 gene located in 11p15 in therapy-related leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 7; Cyclophosphamide; Doxorubicin; Humans; Immunohistochemistry; Karyotyping; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasms, Second Primary; Prednisone; Stomach Neoplasms; Translocation, Genetic; Vincristine

The patient was a 74-year-old man with extremely advanced gastric cancer. A CT scan of the abdomen showed enlargement of many huge abdominal para-aortic lymph nodes. Neoadjuvant chemotherapy (NAC) was planned in order to reduce or eliminate the tumor. Two cycles of FLP combination therapy (5-fluorouracil, leucovorin, cisplatin) were given. After NAC, a CT scan revealed marked shrinkage of the No. 16 lymph nodes, and a distal gastrectomy with extended radical lymph node dissection including the No. 16 nodes was performed. The histological effect was judged to be grade 2. There were no viable cancer cells in the No. 16 lymph nodes. The FLP combination therapy as NAC was so effective that it induced downstaging from stage IVb to IIIb.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Male; Neoplasm Staging; Stomach Neoplasms; Tomography, X-Ray Computed

The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy vs. UFT (a combination of uracil and tegafur), on patient survival and recurrence following surgery for advanced gastric carcinoma.. Between July 1990 and June 1998, a total of 54 patients with advanced gastric cancer were treated postoperatively by adjuvant chemotherapy using MFL or UFT. Surgical treatment was performed according to standardized procedures for radical resection of gastric cancer. The patients were stratified into two groups following surgery. The MFL regimen consisted of methotrexate (100 mg/m2) and 5-fluorouracil (600 mg/m2) at hour 3, followed by leucovorin rescue. The oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance.. In stage 3 gastric cancer, the overall survival rates following surgery was significantly (p < 0.05) higher in the MFL than the UFT group. Difference in disease free survival was not statistically significant between the groups. Recurrence rates showed a trend (p = 0.08) to decrease in the MFL than the UFT group. In stage 4 gastric cancer, no significant difference was obtained in the overall survival rates between the groups.. The present results suggested the superiority of MFL treatment for improving postoperative survival in patients with advanced gastric cancer, in particular for those patients with a high risk of recurrence following potential curative resection. In patients with stage 4 gastric cancer, however, MFL treatment showed similar effects as UFT on the postsurgical survival of the patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation.. In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism.. Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC.

Topics: Algorithms; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Diagnosis, Differential; Disseminated Intravascular Coagulation; Etoposide; Female; Fluorouracil; Hemorrhagic Disorders; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Precancerous Conditions; Stomach; Stomach Neoplasms; Thrombocytopenia

Many studies connected with different aspects of the quality of life (QL) have been increasingly reported. In this study we have been used FACT questionnaire to estimate QL in three groups of cancer patients receiving chemotherapy. Questionnaires were completed by 177 patients. Adverse effects of treatment severely influence the cancer patients QL. The most significant worsening of QL was noticed in the group of lung cancer patients receiving the most emetogenic chemotherapy(i.e. cis-platinum, vepesid). In other two groups (gastric and colorectal cancer patients) side effects of chemotherapy caused relatively less QL deterioration. This finding implicates possibility of intensifying the course of treatment (dosage and duration) assuming there is no hematopoetic insufficiency.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cisplatin; Colorectal Neoplasms; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasms; Quality of Life; Stomach Neoplasms; Surveys and Questionnaires

The therapeutic effect of antibodies raised by the immunogen Gastrimmune was compared with both a CCKB/gastrin receptor antagonist, CI-988, and 5-Fluorouracil/leucovorin in a gastric cancer model. The human gastric ascites cell line, MGLVA1asc, produced and secreted progastrin and glycine-extended gastrin as determined by radioimmunoassay and immunocytochemistry. Cells were also stained with an antiserum directed against the human CCKB/gastrin receptor. MGLVAI asc cells were injected i.p. into SCID mice. Antibodies raised by Gastrimmune immunization of rabbits (affinity for G17 of 0.15 nM and GlyG17 of 0.47 nM) were passively infused i.p. and significantly enhanced survival by up to 5 days (p=0.0024 from vehicle controls). The enhancement in survival was not significantly different from that achieved by treatment with 5-Fluorouracil and leucovorin. A CCKB/gastrin receptor antagonist, CI-988, did not affect survival with cells injected at 7.5 x 10(5) cells/mouse but significantly increased the survival of mice injected with a lower cell innoculum of 5 x 10(5) cells/mouse from 30 to 35 days (p=0.0186). At this lower innoculum antibodies raised by Gastrimmune induced complete survival in 2 animals with the remaining dead by day 36 (p=0.0022). Thus, both endocrine and autocrine pathways mediated by precursor and mature gastrin molecules may be jointly operational in the gastric cancer scenario and may be important targets for therapeutic agents.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cancer Vaccines; Diphtheria Toxoid; Fluorouracil; Gastrins; Humans; Leucovorin; Mice; Mice, SCID; Severe Combined Immunodeficiency; Stomach Neoplasms; Tumor Cells, Cultured

To evaluate the effect of N-phosphonacetyl-L-aspartate (PALA), folinic acid (FA), and interferon alfa (IFN-alpha) biomodulation on plasma fluorouracil (5FU) pharmacokinetics and tumor and liver radioactivity uptake and retention after [18F]-fluorouracil (5-[18F]-FU) administration.. Twenty-one paired pharmacokinetic studies were completed on patients with colorectal, gastric, and hepatocellular cancer, utilizing positron emission tomography (PET), which allowed the acquisition of tumor, normal tissue, and plasma pharmacokinetic data and tumor blood flow (TBF) measurements. The first PET study was completed when the patient was biomodulator-naive and was repeated on day 8 after the patient had been treated with either PALA, FA, or IFN-alpha in recognized schedules.. TBF was an important determinant of tumor radioactivity uptake (r = .90; P < .001) and retention (r = .96; P < .001), for which radioactivity represents a composite signal of 5-[18F]-FU and [18F]-labeled metabolites and catabolites. After treatment with PALA, TBF decreased (four of four patients; P = .043), as did tumor radioactivity exposure (five of five patients; P = .0437), with no change in plasma 5FU clearance. With FA treatment, there were no differences observed in whole-body metabolism, plasma 5FU clearance, or tumor and liver pharmacokinetics. IFN-alpha had measurable effects on TBF and 5-[18F]-FU metabolism but had no apparent affect on liver blood flow.. The administration of PALA and IFN-alpha produced measurable changes in plasma, tumor, and liver pharmacokinetics after 5-[18F]-FU administration. No changes were observed after FA administration. In vivo effects may negate the anticipated therapeutic advantage of 5FU biomodulation with some agents.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Area Under Curve; Aspartic Acid; Colorectal Neoplasms; Drug Interactions; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoplasms; Phosphonoacetic Acid; Regional Blood Flow; Stomach Neoplasms; Tomography, Emission-Computed

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Methotrexate; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms

A 69-year-old man, who had undergone distal gastrectomy for Borrmann type 3 gastric cancer two years ago, experienced a recurrence of multiple liver metastases. Then intra-arterial hepatic cannulation connecting to a subcutaneously implanted port system was indwelt via left subclavial artery. Mitomycin C (20 mg) was injected through out the induced hypertension (1.5 times of his median blood pressure) with intravenously-administered angiotensin II (Delivert), and 5-FU (250 mg/day) was continuously followed for 5 days. He received a total of five courses of this treatment every 4 to 7 weeks. The liver metastases disappeared on CT scan after 4 courses, and a complete response (CR) has been maintained with no use of other chemotherapy. The patient has obtained good quality of life for 32 months after the start of this chemotherapy. Induced hypertensive chemotherapy could be one of the effective treatments for liver metastases from gastric cancer.

Topics: Aged; Angiotensin II; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Injections, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Methotrexate; Mitomycin; Neoplasm Recurrence, Local; Stomach Neoplasms; Vasoconstrictor Agents

A 73-year-old woman was admitted to our hospital in June 1998, suffering from upper abdominal pain. The upper G-I series and endoscopic examination revealed stenosis of the pylorus and antrum by a type 2 cancer, and a poorly differentiated adenocarcinoma and a signet-ring cell carcinoma were confirmed on endoscopic biopsy. A CT scan showed the enlargement of many regional and abdominal para-aortic lymph nodes. FLP therapy combined with cisplatin (50 mg/m2 drip i.v., day 1-8), 5-fluorouracil (333 mg/m2 drip i.v.) and leucovorin (30 mg/body i.v., day 1-8) was planned for neoadjuvant chemotherapy (NAC) in order to reduce or eliminate the tumor and increase curability. After two cycles of the FLP therapy, the tumor size shrunk remarkably and the enlargement of the para-aortic lymph nodes disappeared. Distal gastrectomy with extended lymphadenectomy and cholecystectomy was performed. The histological findings of the primary tumor and metastatic lymph nodes demonstrated massive cancer cell degeneration such as pycnosis and vacuolation, xanthogranulomatous inflammation and dense fibrosis. The effect of NAC was judged to be grade 2 histologically. FLP therapy is an effective and safe regimen for NAC.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Carcinoma, Signet Ring Cell; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Stomach Neoplasms

Although preoperative chemotherapy for advanced gastric cancer is now commonly applied with favorable results, convincing evidence for life prolongation and predictive markers for a good prognosis are both lacking. We report here 5 cases that have shown a distinct positive effect of preoperative chemotherapy together with the results of a precise histological examination of materials indicating features predicting a favorable outcome.. A total of 18 patients with a far-advanced gastric carcinoma subjected to gastrectomy after FLEP (5-fluorouracil, leucovorin, etoposide, cisplatin) in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, could be divided into two distinct groups: 5 surviving over 5 years (group A) and 13 who died within 13 months (group B). Histological features (subtypes) of the carcinomas and chemotherapeutic effects were studied with reference to biopsy materials and resected stomachs and lymph nodes.. In group A, 3 of 5 patients had solid-type poorly differentiated adenocarcinomas. In contrast, in group B, 9 had tubular adenocarcinomas (well or moderately differentiated) and 3 non-solid or diffuse-type poorly differentiated adenocarcinomas and there was only one solid-type tumor. In group A, remarkable therapeutic effects were apparent histologically in 4 of the 5 patients with almost complete disappearance of cancer cells from metastases in lymph nodes, whereas no such changes were evident in group B.. FLEP is distinctly beneficial for certain types of advanced gastric carcinoma, especially solid-type poorly differentiated adenocarcinomas, and favorable results can be predicted, to a certain extent, on the basis of findings for the material resected after chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Combined Modality Therapy; Drug Therapy, Combination; Etoposide; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prognosis; Retrospective Studies; Stomach; Stomach Neoplasms; Survival Analysis; Time Factors; Treatment Outcome

Since adenocarcinoma of the esophagus and cardia is increasing at an alarming rate, major efforts are currently oriented to identify patients who may benefit from extensive resection. Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In six patients (10.2%) with Barrett's adenocarcinoma, cancer was discovered during endoscopic surveillance program for Barrett's metaplasia. Overall, one hundred-forty-seven patients (67%) underwent resection. Fifty-one underwent an extended mediastinal lymphadenectomy. Median cumulative survival was 25.9+/-3.1 months in patients undergoing resection, and 7+/-1.3 months in patients having palliation (p<0.01). Survival was significantly longer in patients with negative nodes than in those with lymph node metastases (54+/-12.9 versus 17+/-2.8 months, p<0.01). Six of the 51 patients (11.8%) undergoing extended lymphadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curve, paracardial, peripancreatic, or lower mediastinal nodes. Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Barrett Esophagus; Cardia; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Diagnostic Imaging; Epirubicin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Fluorouracil; Gastroesophageal Reflux; Humans; Italy; Leucovorin; Life Tables; Lymph Node Excision; Lymphatic Metastasis; Mediastinum; Neoadjuvant Therapy; Neoplasm Staging; Palliative Care; Postoperative Complications; Retrospective Studies; Stomach Neoplasms; Survival Analysis

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Peritoneal Neoplasms; Preoperative Care; Prognosis; Stomach Neoplasms

A 64-year-old man underwent total gastrectomy and placement of the hepatic arterial catheter for advanced gastric cancer with multiple liver metastasis. After the operation, repeated hepatic arterial infusion chemotherapy was performed. Treatment consisted of a 5-day course of continuous arterial infusion of 5-FU. (500 mg/body), leucovorin (21 mg/body) intravenous infusion at 4:00 p.m. on days 1-5, mitomycin C (2 mg/body) arterial infusion at 9:00 a.m. on day 5, and cisplatin (40 mg/body) arterial infusion at 4:00 p.m. on day 5. A total of 13 courses of this chemotherapy diminished liver metastasis. During this therapy, the patient's condition was good, with no experience of nausea or leukopenia.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Circadian Rhythm; Cisplatin; Drug Administration Schedule; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Mitomycin; Stomach Neoplasms

Acute disseminated intravascular coagulation (DIC) is a severe complication of gastric adenocarcinoma, and most of the patients die within 1-3 weeks. We have treated five such patients with an empirical non-myelosuppressive HDFL regimen (weekly 24h infusion of high-dose 5-fluorouracil 2600 mg/m2 and leucovorin 300 mg/m2). Within 2 weeks of starting the treatment the clinical and laboratory evidence of acute DIC quickly resolved in all five patients. HDFL not only caused no further myelosuppression, but also resulted in normalization of the patient's haemogram within a few weeks. Other anti-cancer drugs could then be safely added. Three patients had a survival time of more than 6 months. We suggest that HDFL is an ideal initial treatment for gastric cancer complicated by acute DIC.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Disease-Free Survival; Disseminated Intravascular Coagulation; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

An advanced gastric cancer patient with T3N1M0 successfully underwent a curatively total gastrectomy combined with distal pancreatectomy and lymphnode dissection following ELF-P combined chemotherapy. The patient received two courses of etoposide (75 mg/m2, Day 1-5, i.v.), leucovorin (30 mg/body, Day 2-5, i.v.), 5-FU (500 mg/m2, Day 2-5, i.v.) and CDDP (60 mg/m2, Day 1, i.v.). A partial response for the primary lesion and lymphnode metastasis was obtained, and a successful curative resection of the stomach was performed. No drug adverse responses occurred. The effect of ELF-P chemotherapy was confirmed with grade 1b by histopathological examinations. Neoadjuvant chemotherapy with ELF-P may be useful as an inductive approach for advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Etoposide; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Stomach Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Epirubicin; Female; Fluorouracil; Gastrectomy; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Lymph Node Excision; Male; Middle Aged; Mitomycin; Preoperative Care; Stomach Neoplasms

Recent data have suggested enhanced therapeutic activity with prolonged administration of both etoposide as well as fluoropyrimidines in the treatment of gastrointestinal malignancies. Based on this rationale, we investigated the clinical effectiveness and tolerance of an oral modification of the widely applied etoposide, leucovorin and 5-fluorouracil (ELF) regimen in patients with advanced gastric cancer. 32 patients with advanced gastric cancer were treated with oral etoposide (100 mg), leucovorin (3 x 100 mg), and tegafur (3 x 200 mg) over 14-21 days for a maximum of six cycles. Objective response was seen in only 5 patients (16%), stable disease was documented in 7 (22%), while the remaining patients progressed during therapy. The median time to progression was 2.8 months (range 0.7-12 months) and median overall survival was 6 months (range 1-18+ months). Due to grade 3 nausea/emesis, 8 patients discontinued treatment prematurely, while 12 patients experienced anorexia and progressive weight loss. Haematological toxicity was modest, with 4 patients developing asymptomatic grade 3-4 granulocytopenia. We conclude that this oral combination regimen cannot be recommended for the treatment of advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Stomach Neoplasms; Tegafur; Treatment Outcome

The chemotherapy combining 5-FU, CDDP, and LV was conducted in 17 patients with advanced and recurrent gastric cancer. The regimen consisted of 5-FU (by continual infusion 600 mg/m2/day for 5 days), CDDP (low-dose consecutive drip infusion, 2 hours 20 mg/m2/day for 3 days) and LV (by bolus infusion 20 mg/ m2/day for 5 days). Advanced gastric cancer was found in 12 cases (operation performed in 9 cases and 7 cases resectable) and recurrent in 5 cases. Macroscopic judgment of efficacy in 10 recurrent and inoperable cases revealed CR in 1 patient, PR in 5 patients, NL in 2, and PD in 2 patients. The overall response rate was 60.0%. There were 7 resectable cases, 4 PR patients, 1 MR and 2 NC patients. The overall response rate was 57.1%. Operations were done in 9 of 12 patients with advanced gastric cancer. The histological effects in 7 cases with resectable cases were as follows: 1 patient of grade 0, 2 patients of grade 1a, 3 patients of grade 1b, and 1 patient of grade 2. The main adverse reactions were gastrointestinal symptoms, but in 3 cases thrombocytopenia was found. This chemotherapy for advanced and recurrent gastric cancer shows excellent clinical efficacy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms

The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer.. Patients with locally advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4-9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m2, with dose escalation planned in 25-mg increments, depending on patient tolerance.. Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m2. One patient experienced Grade 4 anorexia and nausea. No other Grade > or = 3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade > or = 4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity.. In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5-fluorouracil (150 mg/m2 daily), leucovorin (10 mg orally daily), and radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.

Topics: Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Pancreatic Neoplasms; Pilot Projects; Stomach Neoplasms

We herein present a case of a 70-year-old man with the tentative diagnosis of far-advanced gastric cancer supposed to be beyond surgical intervention. Neoadjuvant chemotherapy enabled us to perform subtotal gastrectomy with curative intent. The man was admitted to our hospital with the chief complaint of poor appetite. Because preoperative examinations revealed a mass adjacent to the portal vein and common bile duct, which was suspected to be lymphnode metastasis or gastric cancer directly invading those vital structures, 4 weeks of neoadjuvant combination chemotherapy (NACC) (CDDP 10 mg/body, day 1 through day 5/week, UFT 600 mg/body, every day, Leucovorin 15 mg/body, every day) was given with resultant curative resection of the tumor one month after completion of NACC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Leucovorin; Male; Neoplasm Invasiveness; Portal Vein; Stomach Neoplasms; Tegafur; Uracil

Intra-arterial infusion chemotherapy combined with leucovorin (LV) and 5-fluorouracil (5-FU) was performed in two patients with multiple metastases from rectal and gastric cancer. In each patient LV 45 mg was infused as a bolus just before and after 5-FU 1,000 mg/4 hrs administration. Thereafter 5-FU dose was decreased gradually. This regimen was principally repeated weekly on an outpatient basis. In both patients PR was detectable 3 and 4 months after the beginning of chemotherapy, and CR was obtained in 21 and 6 months, respectively. Neither patient showed any signs of recurrence and are in good health 35 and 30 months after initiation of chemotherapy. These findings suggest that our protocol has an excellent anti-tumor effect and improves the QOL in some patients for a long time.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Stomach Neoplasms

The results of chemotherapy against gastric cancer or esophageal squamous cell carcinomas cannot be generalized to adenocarcinomas of the esophagus. Therefore the combination of 5-fluorouracil and folinic acid was studied in esophageal adenocarcinoma.. After a loading dose of 4 x 90 mg folinic acid orally, a continuous infusion of 5-fluorouracil 500 mg/sqm/day for 5 days with concommitant folinic acid 6 x 60 mg/day orally, was administered to 29 consecutive patients with metastatic adenocarcinoma of the esophagus or esophagogastric junction area.. This schedule was tolerated well with mild mucositis and diarrhea. In one patient reversible cardiotoxicity was seen. Five patients obtained a partial remission (19%; 95% confidence interval (CI): 6%-38%), and 8 patients stable disease. One early death.. This combination has modest activity against adenocarcinoma of the esophagus; its toxicity profile permits incorporation in combination protocols.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Drug Therapy, Combination; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Rate; Treatment Outcome

The aim of this study was to evaluate the effect of 5-fluorouracil (5-FU) and folinic acid on liver function and bile production in patients with recurrent gastric cancer and jaundice. Thirteen patients were studied for liver function and hyperbilirubinaemia, and six patients were studied for bile production retrospectively, who were treated with 5-FU [700 mg m(-2)] and folinic acid [20 mg m(-2)] for 4 days. Serum total bilirubin, aspartate aminotransferase (AST), gamma-glutamyl transferase (gamma-GT) and alkaline phosphatase (ALP) concentrations all improved with treatment (P<0.0001), and bile production increased significantly (P<0.0001) following treatment. 5-FU and folinic acid can significantly improve jaundice and liver function, and promote bile production. It is possible that 5-FU and folinic acid may become a new method for the relief of jaundice in patients with gastrointestinal tract malignancies.

Topics: Adult; Aged; Antidotes; Antineoplastic Agents; Bile; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Female; Fluorouracil; Humans; Jaundice; Leucovorin; Liver; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms

A 59-year old man was diagnosed as having advanced gastric cancer, liver metastasis and lymph node metastases after a closed medical examination. Because Schnitzler metastasis was also suspected, chemotherapy was started pre-operatively. The schedule of administration was as follows. One course was l-LV 250 mg/m2 and 5-FU 600 mg/m2 injected intravenously every week and continued for 6 weeks. The UGI examination showed partial response in stomach cancer, and liver metastasis disappeared on CT-scan after 2 courses. We performed total gastrectomy, lymphadenectomy, splenectomy and partial resection of liver. Histological effects showed Grade 1a on main tumor, Grade 2 on liver metastasis, and No. 3 lymphnode metastasis. The survival time was 476 days.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Fluorouracil; Gastrectomy; Hepatectomy; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

A 62-year-old man having advanced gastric carcinoma with extended lymph node metastases was successfully treated by a palliative gastrectomy and 6 courses of sequential methotrexate/5-fluorouracil therapy. No side effects were observed, and all enlarged abdominal lymph nodes disappeared. The complete response has continued for 11 months after the initial treatment.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Remission Induction; Stomach Neoplasms

We performed FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide, and cisplatin) by hepatic artery injections for three patients with multiple liver metastases from gastric cancer, and two of three resulted in partial response (PR). We presented two PR cases. Case 1 is a 57-year-old male with multiple liver metastases from gastric cancer. Distal partial gastrectomy with regional lymphadenectomies were carried out, and an injection port was implanted in the hepatic artery. We performed FLEP chemotherapy from 16 days after the operation. Liver metastases subsided and resulted in PR after 3 months by CT scan. He is now healthy and working for 15 months after the operation. Case 2 was a 49-year-old female with multiple liver metastases from gastric cancer. Total gastrectomy with regional lymphadenectomies was carried out. We performed FLEP chemotherapy by hepatic artery injections from 21 days after the operation. The response of chemotherapy resulted in PR by CT scan, and she is now healthy and has been working for 11 months after the operation. Thus, this form of chemotherapy may be useful for patients with multiple liver metastases from gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Etoposide; Female; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Stomach Neoplasms

We reported a case of gastric cancer with peritoneal dissemination, which was successfully treated by neoadjuvant chemotherapy and partial gastrectomy. A 71-year-old female visited to our hospital because of umbilical tumor (Sister Mary Joseph's node). UGI series showed a Borrmann 1 type gastric cancer and laparoscopic examination revealed peritoneal metastasis. Her abdominal cavity was treated with MTX and CDDP and she was given intravenous administration of 5-FU/LV. Repeated laparoscopy revealed complete disappearance of peritoneal seeding, and a partial gastrectomy was done. The histopathological findings of resected specimen showed the significant effects of preoperative chemotherapy. She has been living for more than 2 years with no recurrence after initial chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Methotrexate; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Tegafur; Uracil

We report a case of a 67-year-old male patient who experienced multiple liver metastasis 6 months after undergoing an operation for remnant gastric cancer. The histological classification of the cancer in gastric remnant was poorly-differentiated adenocarcinoma. The patient was treated with a low dose of LV.5-FU once a week and oral UFT as an outpatient. As a result, after 3 months of the treatment, CT showed that multiple liver lesions almost disappeared, a condition that lasted about 3 years without relapse. Toxic effects due to this treatment were temporary slight liver disfunction, mild anorexia and stomatitis. This case indicates that the regimen of LV.5-FU+UFT may be effective for multiple liver metastasis from postoperative remnant gastric cancer, enabling the patient to maintain an excellent QOL (quality of life).

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Neoplasm, Residual; Stomach Neoplasms; Tegafur; Uracil

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

We describe 53 patients with primary gastric non-Hodgkin's lymphoma (38 stage IE,15 stage IIE) treated with surgery as a primary procedure. According to the Working Formulation, 13 cases had low, 21 had intermediate and 19 had high grade malignancy. 34 patients considered at high risk received postoperative polychemotherapy. The overall 10-year disease-related survival is 91%. Median follow-up is 52 months. 7 patients relapsed (13%). The 10-year disease-free survival rate of the 19 patients initially treated with surgery is 60%, as compared with 92% in the patients who also received chemotherapy (P = 0.004). However, overall survival did not differ between the two groups, since two-thirds of the patients who relapsed after surgery alone were rescued with chemotherapy. Stage, age, sex and histology did not correlate with survival. In our experience, surgery was an adequate first step procedure; the addition of chemotherapy significantly reduced relapses and increased the disease-free survival rate in patients with unfavourable prognostic factors.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Stomach Neoplasms; Vincristine

5-Fluorouracil (5-FU) is an antimetabolite frequently used in the treatment of cancer. The most common adverse reactions are acute gastrointestinal effects and bone marrow suppression while neurological, ocular and dermatological toxicities are unusual. Several cutaneous manifestations can be found. They are hyperpigmentation, maculo-papular eruption and palmar-plantar erythrodysesthesia (PPES) promptly reversed with discontinuation of 5-FU. The etiopathogenesis of such manifestations is still unknown particularly as regards PPES, but it has been postulated that the local drug accumulation secondary to different scheduling (continuous infusion instead of bolus infusion), the total amount of drug, alcoholism, local trauma, increased blood flow could be responsible for them. In this study we have reported 10 cases of dermatological toxicity (1 of these had PPES) observed from January '91 to December '93 in 81 patients treated with bolus injection of 5-FU containing combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Dose-Response Relationship, Drug; Erythema; Female; Fluorouracil; Foot Dermatoses; Hand Dermatoses; Humans; Leucovorin; Male; Middle Aged; Skin Diseases; Stomach Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms

To test if the incorporation of 5-fluorouracil (5-FU) and leucovorin in a modified etoposide, doxorubicin, cisplatin (EAP) regimen could diminish its toxicity and improve its efficacy, 18 patients with far-advanced, unresectable gastric cancer, diagnosed at National Taiwan University Hospital between January 1991 and December 1992, were treated with a FAPEL combination chemotherapy. The regimen consisted of doxorubicin 25 mg/m2 i.v. on day 1, cisplatin 60 mg/m2 i.v. infusion on day 1, etoposide 60 mg/m2/day i.v. infusion on days 1-3, 5-fluorouracil 500 mg/m2/day i.v. on days 1-3, and leucovorin 50 mg/day i.v. on days 1-3; repeated every three to four weeks. The patients included nine metastatic, six locally advanced and inoperable, and three post-gastrectomy recurrent cancer patients with median Karnofsky performance status of 60%. There were 11 men and seven women with a median age of 52.5 years. The patients tolerated the treatment toxicity relatively well and received an average of 4.3 courses of chemotherapy. Most patients completed the protocol therapy except one who refused and another who died of leucopenic sepsis. Myelosuppression was the limiting toxicity, with Eastern Cooperative Oncology Group (ECOG) grade 3-4 leucopenia developing in 35.9% and grade 3-4 thrombocytopenia developing in 11.5% of a total of 78 courses given. The overall objective response rate was 44.4% with 5.5% complete responses and 38.9% partial responses. The overall median survival was seven months (0.5-21 months). The median survival of responders and non-responders was 13 months (5-21 months) and three months (0.5-7 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Stomach Neoplasms

A 75-year-old man with gastric cancer having multiple liver metastases was given intraarterial infusion therapy with sequential low-dose MTX (30 mg/body) and 5-FU (1,000 mg/body) for metastatic liver tumors one month after the primary gastric tumor was resected. This therapy was given once a week on admission and every two weeks while an outpatient. A total of 18 courses of this therapy produced marked regression and necrosis of liver metastases. The effect was thus rated as partial response. This patient survived 15 months after surgery. These results indicate that intraarterial infusion therapy with sequential low-dose MTX and 5-FU may be effective in multiple liver metastasis from gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Methotrexate; Stomach Neoplasms

We performed combination chemotherapy consisting of 5-FU, leucovorin, and CDDP (FLP therapy) against noncurative resected or recurrent stomach cancer in outpatients as of August 1991. Seventeen outpatients patients underwent FLP therapy until February 1993. Therapeutic responses, survival time after the operation or recurrence, rate at home, and the improvement of performance status (PS) were studied. The response rate was 54.5%, median survival time was 410 days, the rate at home was 75.5 +/- 14.7%, and the rate of improvement of PS was 82.4%. Toxicities were observed in 70.6%. Thrombocytopenia must be followed carefully, but it was encountered in only a few patients. FLP therapy for advanced or recurrent stomach cancer in outpatients was expected to improve the QOL.

Topics: Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Furosemide; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Outpatients; Quality of Life; Stomach Neoplasms

A case of an 81-year-old male with Borrmann II type was reported. The lesion was diagnosed histologically as undifferentiated adenocarcinoma. Biochemically modulated chemotherapy preceded by administration of Methotrexate (MTX) and followed by 5-fluorouracil (5-FU) was given to him. The procedure was weekly intermediate-dose therapy consisting of MTX 100 mg (i.v.) followed 3 hours later by 5-FU 600 mg (i.v.) with leucovorin rescue in the following 2 days. After this treatment was repeated 6 times, advanced gastric cancer disappeared on endoscopic and histological findings, so the patient was regarded as showing a complete response. Ths, this biochemically modulated chemotherapy was thought to be in effective method against gastric cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Remission Induction; Stomach Neoplasms

A 65-year-old man complaining of nausea and loss of appetite was diagnosed as having Borrmann type 3 gastric cancer with multiple liver metastasis. He was treated for 5 days with bolus injections of l-leucovorin (l-LV: 100 mg/m2/day) followed by 5-fluorouracil (5-FU; 370 mg/m2/day), and this was repeated every 4 weeks. The computed tomography scan after 3 cycles showed an approximately 70% decrease in the size of metastatic lesions, indicating a partial response. The primary gastric lesion also showed a partial response. There were modest but tolerable side effects such as diarrhea. After 3 cycles, the patient was discharged and was given oral 5-FU preparation. He died 9 months after initial chemotherapy with a response duration of 5 months. This l-LV and 5-FU combination therapy appears useful for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Stomach Neoplasms

A 51-year-old female with inoperable gastric cancer and with infiltration of pancreatic tail diagnosed by abdominal CT was treated with leucovorin (LV) and 5-fluorouracil (5-FU). The regimen was: LV 30 mg/body/24 hr prior to 5-FU 1,000 mg/m2/day for 48 hrs. This treatment was repeated 6 times. After treatment, the size of tumor decreased so that the patient was able to be operated (Total gastrectomy with partial distal pancreatico-splenectomy). During the treatment, patient showed no side effect except for slight nausea. This neo-adjuvant chemotherapy might be a recommendable treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Middle Aged; Stomach Neoplasms

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Leucovorin; Mice; Mice, Nude; Neoplasm Transplantation; Stomach Neoplasms

The biochemical modulation of 5-fluorouracil (5-FU) and leucovorin (LV) has resulted in a remarkable increase of the response rate in patients with colorectal cancer. Recently, in the treatment of gastric cancer this biochemical modulation has been introduced into clinical practice and has also achieved good antitumor activity. A review of the literature indicates that 5-FU/LV therapy for gastric cancer is effective only when LV is administered at high doses (200 mg-500 mg/m2), and the efficacy of low dose LV (20 mg/m2) administration with the combination of high dose 5-FU is still unknown. Thirty-five patients with measurable recurrent gastric cancer received low dose LV and high dose 5-FU for 4 days. The schedule was as follows: iv injection of low dose leucovorin (20 mg/m2) and from one hour later 2-hour infusion of high dose 5-FU (700 mg/m2). This new treatment for recurrent gastric cancer achieved a response rate of 40.0%, and 80.0% of the patients with pronounced palliative effects measured as recurrence-related symptoms. It is very rare for 7 out of 8 patients (87.5%) to be relieved of obstructive jaundice, and we now prefer this therapy to percutaneous transhepatic biliary drainage in patients with jaundice. The toxicity of this biochemical modulation is leukopenia, stomatitis and diarrhea, and the number of patients with toxicity over grade 3 was 5 (14.3%). There was no treatment-related death.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Rate

Various factors, including thymidylate synthase, thymidine kinase, 5-fluorouracil phosphorylation and degradation pathways, folate concentrations, and the stability of ternary complex, which influence thymidylate synthase inhibition rate of fluoropyrimidines, were studied in 87 human adenocarcinoma tissues.. The activity of the 5-fluorouracil degradation pathway was not significantly lower than the activity of the 5-fluorouracil phosphorylation pathway. The activity of the catabolism pathway of 5-fluorouracil should be considered in human adenocarcinoma tissue during chemotherapy. On the other hand, the means plus or minus standard deviations (means +/- SD) of the concentration of 5,10-methylenetetrahydrofolate and tetrahydrofolate were 0.69 +/- 0.54 and 1.25 +/- 0.69 nM, respectively, for the adenocarcinoma tissues without previous chemotherapy.. Because the half-life of tritium-labeled ternary complex and folate concentration in cytosol were correlated well, the differences in folate concentration among tumors must influence the dynamic equilibrium of ternary complex formation. Moreover, these results show that the ratio of 5,10-methylenetetrahydrofolate concentration to thymidylate synthase concentration influences the thymidylate synthase inhibition rate in tumor, and that the new synthesis of 5,10-methylenetetrahydrofolate and tetrahydrofolate from other endogenous reduced folates is also important in tumors with high thymidylate synthase concentrations.

Topics: Adenocarcinoma; Colorectal Neoplasms; Culture Techniques; Fluorouracil; Folic Acid; Humans; Leucovorin; Lymph Nodes; Phosphorylation; Stomach Neoplasms; Tetrahydrofolates; Thymidine Kinase; Thymidylate Synthase

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Preoperative Care; Prognosis; Stomach Neoplasms

Twenty-four patients with advanced or relapsed gastric or colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), leucovorin (LV) and interferon-alpha (IFN-alpha). 5-FU was administered by rapid intravenous infusion at 350 mg/m2 for 5 consecutive days. Intravenous bolus administration of LV 20 mg/m2 was given before each 5-FU administration. This combination was repeated every 3 to 4 weeks. IFN-alpha (HLBI), 6MU, was administered subcutaneously daily. Of 13 patients with gastric cancer, there were 2 PR, 4 NC and 7 PD, and among 11 patients with colorectal cancer, there were 1 CR, 8 NC and 2 PD. All 16 previously treated patients had no clinical response. Responses were seen in patients with no prior chemotherapy and with good performance status. Most common toxicities observed were leucopenia, fever, stomatitis and diarrhea, which were all tolerable and reversible.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Subcutaneous; Interferon-alpha; Leucovorin; Male; Middle Aged; Stomach Neoplasms

In a 63-year-old male patient with gastric cancer having multiple liver metastases, the metastatic lesions responded well to postoperative staggered intraarterial infusion therapy with MTX and 5-FU. The intraarterial infusion therapy was administered once a week. A total of 5 courses of this therapy produced marked regression of liver metastases and remarkable necrosis. The effect was thus rated as PR. The patient is healthy and has been successfully rehabilitated. His dose is oral 5-FU (200 mg x 2).

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Methotrexate; Middle Aged; Remission Induction; Stomach Neoplasms

The patient was a 44-year-old male with gastric cancer accompanied by pancreatic invasion and metastasis to the periaortic lymph nodes. Combination chemotherapy with 5-FU, leucovorin (LCV) and CDDP (FLP therapy) was preoperatively given. Pancreaticoduodenectomy was carried out as absolutely noncurative resection. FLP therapy was continued postoperatively, and resulted in disappearance of the metastases in the periaortic lymph nodes on CT. As there were no findings of recurrence, the patient was regarded as being in complete response. In addition, the performance status improved from Grade 2 to Grade 0. Since the three-drug combination therapy induced only slight adverse reactions (Grades 1-2), it could be safely carried out at the outpatient department. Thus, combination therapy with 5-FU, LCV and CDDP is thought to be effective against gastric cancer.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Pancreatic Neoplasms; Remission Induction; Stomach Neoplasms

Surgical neoadjuvant therapy for gastric adenocarcinoma affords the opportunity to evaluate critically the histologic effects of preoperative chemotherapy.. Morphologic alterations in gastric adenocarcinomas were examined in the surgical-resection specimens from 25 patients after 6 weeks of preoperative chemotherapy. The group included 1 patient with a complete response; 4, with subtotal responses; 4, with partial responses; and 16, with no response to preoperative chemotherapy.. Histologic manifestations of preoperative chemotherapy included mucosal edema, aggregates of histiocytes in the submucosa and muscularis externa, and stromal fibrosis of the submucosa and muscularis externa. Cytologic manifestations were uncommon and included a single case of signet ring cell carcinoma with diminution of the cytoplasmic vacuoles after preoperative chemotherapy. Clinical follow-up was limited, but 3 of the 25 patients died within 5-8 months after the diagnosis of gastric adenocarcinoma. The gastric-resection specimens from these three patients did not show any histologic manifestations of preoperative chemotherapy.. As in tumors at other sites, the efficacy of surgical neoadjuvant therapy for gastric adenocarcinoma can be assessed, based on the histologic response of the resected tumor to preoperative chemotherapy.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Gastric Mucosa; Histiocytes; Humans; Immunoenzyme Techniques; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Remission Induction; Stomach; Stomach Neoplasms

Leucovorin (LV) increases the cytotoxic effect of fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) by enhancing the formation of the fluorodeoxyuridine monophosphate (FdUMP) thymidylate synthase (TS) 5,10-methylenetetrahydrofolate (mTHF) ternary complex. To study the difference in the efficacy of this combination against different tumors, we compared the effect of LV (20 microM) on the cytotoxicity of FUra, FdUrd, and 5-fluorouridine (FUrd) in vitro against cell lines of five colorectal carcinomas (CC), five gastric carcinomas (GC), and four non-small-cell lung carcinomas (NSCLC) using the colony-forming assay. At the concentration used in the experiments, LV alone failed to inhibit colony formation in any of the cell lines tested. The NSCLC cell lines were more resistant to FdUrd than were the CC and GC lines. LV modulated the cytotoxicity of FdUrd in all five CC lines and in three of the five GC lines but failed to do so in any of the NSCLC lines. In addition, following 20 h treatment with 1 microM [3H]-FdUrd, formation of the FdUMP/TS/mTHF ternary complex was enhanced by LV in the LV-sensitized CC and GC cell lines but not in the LV-refractory NSCLC lines. These in vitro data corresponded well to the results of clinical trials. Therefore, the colony-forming assay may be useful for the identification of the sensitivity of tumors according to phenotype.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Cell Survival; Colony-Forming Units Assay; Colorectal Neoplasms; Drug Synergism; Floxuridine; Fluorodeoxyuridylate; Fluorouracil; Leucovorin; Lung Neoplasms; Stomach Neoplasms; Tetrahydrofolates; Thymidylate Synthase; Tumor Cells, Cultured

Potentiation of cytotoxic effects of 5-fluorouracil (5-FU) were investigated by simultaneous or sequential combination of l-leucovorin (LV) against human esophageal cancer cell line (TE-1, TE-2) and 23 human clinical cancer samples in vitro. LV enhanced the cytotoxic effects of 5-FU on human esophageal cancer cell line as a dose dependent manner, and increased the cytotoxic effect of 5-FU about 1.5-fold with 10 microM and about 2-fold with 100 microM. The incubation time did not affect the effects. The potentiation with LV was also demonstrated against human clinical cancer samples, and the cytotoxic effects of 5-FU increased 7.6% in esophageal cancer, 20.9% in gastric cancer and 25.5% in colorectal cancer. As a result, the potentiating effects of LV against 5-FU seemed to be limited on human esophageal cancer.

Topics: Colonic Neoplasms; Drug Screening Assays, Antitumor; Drug Synergism; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Stomach Neoplasms; Tumor Cells, Cultured

The patient was a 44-year-old female who had Borrmann type 4 gastric cancer with enlarged intra-abdominal lymph node metastasis. L-leucovorin (l-LV, 100 mg/m2/day by intravenous bolus for a period of one minute) and fluorouracil (5-FU, 370 mg/m2/day by intravenous bolus) was administered for 5 consecutive days, with a 28-day interval. Dysphagia was subsided 4 weeks after the initial treatment. After 11 weeks, abdominal lymph node metastasis had been reduced in its size (reduced rate 89%). After 16 weeks, gastric structure were remarkably improved (62.2% enlarged in its focus space) in upper GI X-ray. Therefore, total gastrectomy was performed 20 weeks after the initial combination therapy. She has been alive for the past year after the initial treatment. We concluded a combination therapy of l-LV and 5-FU was effective in this patient.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lymphatic Metastasis; Stomach Neoplasms

Leucovorin and interferon are capable of modulating the cytotoxicity of fluorouracil (5-FU). Preclinical studies demonstrate that d,l-leucovorin is rapidly metabolized in human breast and colon cells into the various one-carbon substituted folate pools and to the polyglutamated state. While increases in intracellular folate pools are proportional to the exposure concentration of leucovorin, relatively large increases in leucovorin concentrations (50- to 100-fold) are required to produce small intracellular changes (twofold). Polyglutamation is favored by prolonged exposures to leucovorin. Polyglutamate forms have a prolonged intracellular retention and a higher affinity for the target enzyme, thymidylate synthase. Ratios of up to 20:1 inactive to active leucovorin stereo-isomers had essentially no effect on the intracellular metabolism of the active isomer. Interferon gamma interacts with 5-FU in H630 colon cancer cells at the level of thymidylate synthase and enhances cytotoxicity of 5-FU by eliminating the 5-FU-induced acute overexpression of the target enzyme. No alterations in the intracellular metabolism or nucleic acid incorporation of 5-FU could be demonstrated with the addition of interferon gamma. A clinical trial combining interferon-alfa-2a (IFN-alpha-2a) (subcutaneous days 1 to 7) with 5-FU and leucovorin (given IV days 2 to 6) demonstrated that these agents could be combined with acceptable toxicity. While the addition of interferon did not allow dose escalation of 5-FU, it resulted in a significant increase in drug exposure (1.5-fold) compared with matched cycles of 5-FU plus leucovorin without interferon. The overall response rate in this pilot study of 13 untreated patients with gastrointestinal adenocarcinoma was 46%, including two complete responses. There were no responses in eight patients who had previously failed therapy with 5-FU.

Topics: Colonic Neoplasms; Colorectal Neoplasms; Drug Administration Schedule; Drug Interactions; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Interferon-gamma; Leucovorin; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Recombinant Proteins; Stomach Neoplasms; Tetrahydrofolates; Tumor Cells, Cultured

The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy a

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Etoposide; Evaluation Studies as Topic; Fluorouracil; Humans; Leucovorin; Prognosis; Stomach Neoplasms; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Doxorubicin; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukin-2; Leucovorin; Methotrexate; Mitomycin; Recombinant Proteins; Stomach Neoplasms

A group of 20 patients with gastric cancer, refractory to or with no change after two or three cycles of carboplatin were treated with etoposide/folinic acid/5-fluorouracil (ELF). An objective remission rate of 45% (9/20), a median remission duration of 8 months and a median survival time of 11 months were achieved. Toxicities were mild to moderate only. These results are comparable to those being achieved with ELF in previously untreated gastric cancer patients and confirm its efficacy and good tolerability.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Etoposide; Fluorouracil; Humans; Leucovorin; Premedication; Remission Induction; Stomach Neoplasms; Time Factors

Ten patients with non-resectable gastric cancer were subjected to a neo-adjuvant chemotherapy (FLEP therapy), consisting of 4 drugs (leucovorin and 5-FU i.v., CDDP and etoposide i.a.) combination therapy from August 1989 to April 1991. The response rate of this therapy with primary lesions, metastatic lymph-nodes (mainly paraaortic lymph nodes), metastatic liver tumor and peritoneal dissemination were 50, 50, 25 and 33%, respectively. Five cases underwent total gastrectomy. Pathological evaluation of these cases was Grade 1 or 2. Side effects were mainly gastrointestinal disturbances, namely stomatitis, nausea, vomiting and anorexia, along with bone marrow suppression. Performance status of these patients improved to a significant degree by the therapy. This therapy seemed to be effective in controlling paraaortic lymph-node metastasis. The advantage of i.a. delivery was investigated by Tc-MAA scintigraphy. The distribution of Tc-MAA after i.a. injection suggested that i.a. chemotherapy enhanced intraabdominal drug concentration. There is no established treatment for far advanced cases, so this therapy seems to be worth a try.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intra-Arterial; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms

A man with previous addiction to parenteral drugs presented infection by human immunodeficiency virus (HIV) with persistent generalised lymph node enlargement. Sixteen months after diagnosis, he developed intermediate-grade lymphoma of the stomach. Partial response was achieved by chemotherapy, and the patient presented pulmonary and meningeal tuberculosis which led him to exitus.

Topics: Adult; AIDS-Related Complex; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Opportunistic Infections; Stomach Neoplasms; Substance-Related Disorders; Tuberculosis, Miliary; Vincristine

We compared the in vitro sensitivity patterns to cytotoxic drugs and expression of the multidrug resistance-associated MDR1 gene (also known as PGY1 gene) in four gastric carcinoma cell lines with those obtained in a panel of 11 colorectal carcinoma cell lines. In addition, we tested the effects of leucovorin on enhancement of fluorinated pyrimidine-induced cytotoxicity. We used a semiautomated tetrazolium dye assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (tetrazolyl blue)] (MTT) to compare the drug sensitivity of the gastric carcinoma cell lines with that of the colorectal carcinoma cell lines. The gastric carcinoma cell lines were more sensitive to some drugs, including doxorubicin and cisplatin, but not to the fluorinated pyrimidines. Addition of leucovorin at a clinically achievable concentration enhanced the cytotoxic effects of both fluorouracil and floxuridine in colorectal carcinoma cell lines, but it enhanced the effects of only floxuridine in gastric carcinoma cell lines. With the use of a slot blot assay, relatively low levels of MDR1 RNA were present in all four gastric carcinoma cell lines, while intermediate or high levels were present in most of the colorectal carcinoma cell lines. In general, our findings reflect clinical experience and may help in the design of clinical trials.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Survival; Colorectal Neoplasms; Drug Resistance; Drug Synergism; Gene Expression; Humans; Leucovorin; Membrane Glycoproteins; RNA, Messenger; RNA, Neoplasm; Stomach Neoplasms; Tumor Cells, Cultured

A 68-year-old woman complaining of severe iron deficiency anemia was found to have an advanced gastric cancer (poorly differentiated adenocarcinoma) with multiple liver metastases. The patients was treated three times with combination chemotherapy using a monthly schedule consisting of bolus infusion of mitomycin C (10 mg/m2) on day 1, continuous infusion of 5-fluorouracil (600 mg/m2) on day 1 to 6, and continuous infusion of high-dose leucovorin (300 mg/body) on day 1 to 6, with concomitant oral administration of dipyridamole (300 mg/day) over 14 days. Endoscopically, cancerous ulcer in the primary gastric lesion improved like a healed peptic ulcer. Metastatic lesions in the liver almost disappeared on computed tomography. The most prominent side effect was oral mucositis which was tolerable and healed in a week. This regimen appears potentially useful in the treatment of gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Mitomycin; Mitomycins; Stomach Neoplasms

Topics: Drug Eruptions; Fluorouracil; Humans; Injections, Subcutaneous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Stomach Neoplasms

The recent successes being achieved with combination chemotherapy regimens, such as FAMTX (fluorouracil [5-FU], doxorubicin, methotrexate), EAP (etoposide, doxorubicin, cisplatin), and ELF (etoposide, leucovorin, 5-FU), strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remissions (CRs). Moreover, some of these CRs were histopathologically confirmed. The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. Thirty-six patients with LAD had been treated in a phase II trial with preoperative EAP, inducing 24 (70%) overall remissions (two clinical CRs, six pathologic CRs, 16 partial remissions [PRs] in 35 evaluable patients. Twenty-one patients were disease-free after chemotherapy with or without second-look surgery. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease-free. The expected survival of patients with unresectable LAD is approximately 4 to 6 months without any treatment and 6 to 9 months with standard chemotherapy. Compared with the latter results, the preoperative use of effective regimens (eg, EAP) seems to improve prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stages IIIa or IIIb). However, partly because of the severe toxicities (myelosuppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens for the following reasons: Two of three patients with gastrointestinal disease are older than 60 years. Nontumorous diseases of the cardiovascular system, kidney, and others are frequent in this age group and may complicate or even prevent treatment with aggressive regimens. Considering the predominantly palliative treatment intentions in far advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination ELF in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Evaluation; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Levoleucovorin; Male; Middle Aged; Prognosis; Remission Induction; Reoperation; Stomach Neoplasms; Survival Rate

The results of different chemotherapeutic regimens used in the treatment of advanced gastric cancer are compared. Three groups of patients were evaluated. The first group (59 patients) was treated by a new regimen consisting of methotrexate, 5-fluorouracil, cyclophosphamide and lederfolin (MFC + CF), the second group (21 patients) was treated by COnFU regimen (cyclophosphamide, vincristine, 5-fluorouracil), and the third group (35 patients) was treated with 5-fluorouracil (5-FU) alone. The control group of 41 patients with advanced gastric cancer was not treated cytostatically. The percentages of positive responses were as follows: 49.2% in the group treated with the new regimen, 33.3% in the COnFU group, and 14.3% in the 5-fluorouracil group. Median survival time of patients treated with the new regimen was significantly longer than that in the control group. Toxicity resulting from the new regimen treatment was moderate. The results of the new regimen can be compared to those obtained by other authors using the FAM regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Mitomycin; Mitomycins; Stomach Neoplasms; Survival Rate

To determine the feasibility and toxicity of combining leucovorin (CF) with a 5-fluorouracil (5-FU) combination chemotherapy regimen currently accepted by many as standard treatment for gastric cancer, CF (500 mg/m2) was administered in combination with the Georgetown 5-FU, doxorubicin, and mitomycin C (FAM) regimen. Thirty-two patients with advanced adenocarcinoma of the stomach were evaluable for toxicity and 26 patients with measurable disease were evaluable for response. Fifty-four percent of patients were previously treated with chemotherapy or radiation therapy. The response rate was 38% (95% confidence interval, 21% to 59%). The median duration of response was 6 months (range, 2 to 23+ months). The estimated median survival time was 6.8 months for patients with measurable disease and 11.5 months for all 32 patients. Although diarrhea is dose limiting when 5-FU and CF are administered weekly for 6 of 8 weeks, diarrhea occurred rarely on this combination regimen with 5-FU and CF administered only 4 of every 8 weeks. The dose-limiting toxicity of FAM-CF was cumulative myelosuppression, which also occurs with the standard FAM regimen. As a result, the administered dose intensity of 5-FU decreased as patients continued on study. Thus, a randomized comparison of FAM with FAM-CF would not determine whether CF modulation increases the efficacy of 5-FU when it is administered in optimal doses to patients with gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Mitomycins; Stomach Neoplasms

Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Etoposide; Female; Fluorouracil; Heart Diseases; Humans; Leucovorin; Male; Middle Aged; Remission Induction; Risk Factors; Stomach Neoplasms; Survival Rate

Topics: Humans; Leucovorin; Lymphoma; Methotrexate; Stomach Neoplasms

We reported 2 patients treated with Methotrexate (MTX)-Fluorouracil (5-FU) sequential therapy combined with Doxifluridine (5'-DFUR). The method of administration was as follows: MTX 60 mg was given intravenously (iv) followed by 5-FU 600 mg iv 2 hours later in colon cancer and 5 hours later in gastric cancer. Leucovorin 20 mg was administered 3 times every 6 hours beginning 6 hours after 5-FU infusion. This cycle was repeated once a week for 5 weeks. 5'-DFUR 1,200 mg was given orally daily and continued after MTX.5-FU therapy. Patient 1 was a 60-yr-old female with recurrent colon cancer developed four years after sigmoidectomy. She was referred to our hospital for further examinations of elevated serum carcinoembryonic antigen (CEA). The enlarged intraabdominal lymph nodes due to recurrence were demonstrated on computer tomography and the chemotherapy was performed as described above. The swelling of lymph nodes showed marked reduction in size and CEA value was normalized. Patient 2 was a 59-yr-old man with advanced gastric cancer accompanied by giant liver metastasis. Both primary and metastatic lesion responded favorably to this regimen. There was no remarkable side effect in either patient. These results suggest that this method is worth performing in further clinical trials for cancer patients.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Colonic Neoplasms; Drug Administration Schedule; Female; Floxuridine; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Stomach Neoplasms

Patients with advanced gastric cancer were treated with methotrexate-5-fluorouracil sequential therapy. In order to rescue of methotrexate toxicity on the normal proliferating tissue, leucovorin was administered orally to outpatients. As the comparative study, we examined plasma kinetics following oral administration of leucovorin (15 mg) in 6 patients with gastric cancer (received subtotal gastrectomy) and 5 normal subjects. In the patients, peak plasma concentrations of d-1-formyltetrahydrofolate and its main metabolite 5-methyltetrahydrofolate were found after 2 hrs. (7.35 X 10(-7) M, 3.09 X 10(-7) M), and in normal controls also both after 2 hrs. (1.01 X 10(-6) M, 4.89 X 10(-7) M). The active folate metabolite persisted for more than 6 hrs. at over 1 X 10(-7) M that could rescue normal tissue from methotrexate toxicity after leucovorin oral administration in the patients received subtotal gastrectomy.

Topics: Administration, Oral; Adult; Biological Assay; Chromatography, High Pressure Liquid; Female; Formyltetrahydrofolates; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Tablets; Tetrahydrofolates

Topics: Adenocarcinoma; Animals; Bone Marrow; Colonic Neoplasms; Deoxyuracil Nucleotides; Fluorodeoxyuridylate; Fluorouracil; Humans; Intestinal Mucosa; Leucovorin; Liver; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Rectal Neoplasms; Stomach Neoplasms; Thymidylate Synthase

In vitro and in vivo studies have been carried out in mouse and human tumors to investigate the biochemical and pharmacologic basis for the selectivity of 5-fluorouracil (FUra) action. Combination chemotherapy with FUra and thymidine was performed to determine the therapeutic relevance of 5-fluorouridine triphosphate (FUTP) incorporation into RNA. The results of these studies indicate that modulation of FUra cytotoxicity by deoxythymidine (dThd) did occur but failed to produce any significant therapeutic advantages in patients with advanced colorectal cancer. Modulation of FUra bioactivation via the deoxyribonucleotide pathway by coadministration of high-dose folinic acid resulted in enhanced therapeutic response rate of gastrointestinal tumor patients. This manuscript summarizes the preclinical and clinical findings on the metabolic modulation of FUra activity by dThd and folinic acid.

Topics: Animals; Biotransformation; Cell Division; Colonic Neoplasms; DNA; Drug Synergism; Fluorouracil; Folic Acid; Humans; Leucovorin; Leukemia L1210; Mice; RNA; Stomach Neoplasms; Thymidine; Thymidylate Synthase

The results of a cooperative study on sequential MTX-5-FU treatment of gastrointestinal cancer were presented. The treatment consisted of three methods, A, B, C. At zero time, MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. infusion were given, and 5-FU 600 mg/m2 (A, B, C) was infused 1-3 hours after MTX in gastric cancer patients and 7 hours afterwards in colorectal cancer patients. Twenty-four hours after MTX, leucovorin rescue of 10 mg/m2 p.o. was given either 0 times or once in A, 6 times in B and 8 times in C every 6 hours. In gastric cancer patients, the response rate was 23.2% of 56 cases in A, 40.5% of 37 cases in B and 0% of 3 cases in C. In colorectal cancer patients, the response rate was 28.6% of 21 cases in A, 20.0% of 15 cases in B and 0% of 3 cases in C. Median survival was 7.4 months (M) in total, 5.5 M in A and 7.6 M in B for gastric cancer, and 8.1 M in total, 10.9 M in A and 7.8 Min B for colorectal cancer. Side effects were mild and tolerable. In summary, in this phase II study on gastric cancer, although the response was limited with A, the relatively high response rate of 40.5% with B was promising. The subsequent phase III study will need to evaluate the biochemical modulation with sequential MTX-5-FU treatment in gastric cancer patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Stomach Neoplasms

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Synergism; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Stomach Neoplasms

Twenty-eight patients with advanced measurable gastric carcinoma were treated with leucovorin (dl-CF; folinic acid; dl-5-formyltetrahydrofolic acid) 500 mg/m2 administered as a two-hour infusion and 5-fluorouracil (5-FU) 600 mg/m2 intravenous (IV) push midinfusion. Treatment was administered weekly for 6 weeks followed by a 2-week rest. Twenty-five patients were evaluable for response. Twelve of them had received previous combination chemotherapy that included 5-FU. Median age was 59 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. Three patients had partial responses and two of them had been treated previously with 5-FU. Twelve patients had stable disease. Five of these patients had subjective improvement with improved performance status and/or decreased dysphagia. The 95% confidence interval for response is 3% to 32%. Median survival time for all 28 patients enrolled in the study was 22 weeks. Toxicity was moderate and consisted primarily of diarrhea. Myelosuppression, skin rash, and increased lacrimation also occurred. Plasma concentrations of the active reduced folates, I-CF and 5-methyltetrahydrofolic acid (5-CH3FH4), were greater than the 10 mumol/L levels that potentiate 5-FU activity in in vitro models, for more than four hours in all five patients in whom pharmacokinetics were studied. 5-FU and high-dose dl-CF has activity in patients with gastric carcinoma including patients who had previously progressed on 5-FU-containing combinations. Further study in a larger patient population is necessary to determine the usefulness of this regimen in gastric carcinoma.

Topics: Adenocarcinoma; Bone Marrow Diseases; Diarrhea; Drug Evaluation; Erythema; Fluorouracil; Humans; Injections, Intravenous; Kinetics; Leucovorin; Middle Aged; Stomach Neoplasms

We report the results of an expanded trial of 5-fluorouracil (FUra) combined with high-dose folinic acid for treatment of patients with advanced colorectal or gastric adenocarcinoma. In each treatment course, the patients received both FUra (340-400 mg/m2/day by iv infusion over 15 minutes) and folinic acid (200 mg/m2/day by iv bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete response (CR) and partial response (PR) rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to FUra attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates above 10(-5) M were achieved after a rapid single iv injection of 200 mg/m2 of folinic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Metabolic Clearance Rate; Rectal Neoplasms; Stomach Neoplasms

Twenty-five patients with advanced measurable gastric carcinoma were treated with D,L-leucovorin (CF) (500 mg/m2) administered as a 2-hour infusion and FUra (600 mg/m2) iv push midinfusion. Patients were treated weekly for 6 weeks followed by a 2-week rest. Median age was 57 (range 32 to 82). Median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0 to 4). Thirteen patients had progressed on previous combination chemotherapy that included FUra. At the time of this report, 19 patients were evaluable for response: 3 patients had partial responses, 8 had stable disease, and 8 progressed (but 3 of these received only 3 or fewer treatments before early disease-related death). Two of the responders were previously treated with FUra. Four patients were too early to evaluate. Measurable responses of greater than 50% were seen in bone, liver, lung, and an abdominal mass. Diarrhea occurred in 9 patients and FUra dose reduction was necessary in 8 of them. Other toxicities included lacrimation, rash, nausea, and mucositis. One toxic death occurred. Nine patients with gastrointestinal tumors confined primarily to the intra-abdominal space were treated with ip FUra in escalating doses (2 mM to 4 mM) in combination with D,L-CF in a 2-liter volume, either by 8 consecutive 4-hour dwells (7 patients) or once daily for 5 days (2 patients). The D,L-CF dose was 20.8 microM except for the first day of the 5-day schedule when it was 104 microM. Toxicity included leukopenia, mucositis, nausea and vomiting, skin rash, and abdominal pain. Three episodes of peritonitis resolved with antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Dose-Response Relationship, Drug; Drug Evaluation; Fluorouracil; Humans; Injections, Intraperitoneal; Leucovorin; Middle Aged; Stomach Neoplasms

Fifteen patients with advanced gastric carcinoma were treated by intraaortic infusion therapy with sequential MTX and 5-FU. Intraaortic bolus injection with 50-100 mg/body MTX was followed 3 hours later with 500-750 mg/body 5-FU and 24 hours later with 30 mg/body leucovorin. Treatment was repeated weekly. Of these 15 patients who were evaluated, 4 had PR and 3 had MR. Response rate was 27%. Two patients had WBC nadir of less than 3,000 cells/mm and other two had a platelet count nadir of less than 10/mm. Gastrointestinal symptoms such as nausea and vomiting were mild. Three patients had diarrhea and 3 had mucositis. No other toxicity was seen. This regimen has been well tolerated for long periods.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Injections, Intra-Arterial; Leucovorin; Male; Methotrexate; Middle Aged; Stomach Neoplasms

Sixty-six patients with advanced colorectal adenocarcinoma and 24 with advanced gastric adenocarcinoma were treated; all had measurable tumors. The treatment was based on biochemical and cell culture studies which have demonstrated that an excess of intracellular reduced folates is necessary to provide optimal inhibition of thymidylate synthetase and to increase the cytotoxic effect of fluoropyrimidines. The treatment comprised 5-fluorouracil (5-FU) (370-400 mg/m2/day) and high dose folinic acid (200 mg/m2/day) given simultaneously for 5 consecutive days with a 21-day interval between courses. Of the 66 patients with colorectal carcinoma, 44 had not been previously treated with cytostatics and 22 were resistant to previous chemotherapy with 5-FU given either as a single agent or combined with other drugs. The response rates both complete (CR) and partial (PR) were 45% and 18% in the previously untreated and the previously treated patients, respectively. Time to disease progression in the 20 previously untreated patients ranged from 2 to 34.5+ months (median, 10.3 months) and that of the 4 patients previously resistant to 5-FU was 7, 10, 12 and 15 months, respectively. Median survival for the 24 responders was 20.4 months. Survival in responders was significantly superior to that observed in patients with progressive disease (P less than 10(-8)). Of the 24 patients with gastric adenocarcinoma, 23 had not been previously treated with cytostatics and one was resistant to a 5-FU containing regimen. The response rate (CR + PR) was 50% (12 patients). The single previously treated patient failed to respond. Time to disease progression in the 12 responders ranged from 2.1 to 28.9 months (median, 5.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms

Topics: Doxorubicin; Fluorouracil; Humans; Leucovorin; Methotrexate; Stomach Neoplasms

In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.

Topics: Adult; Aged; Ambulatory Care; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Probability; Stomach Neoplasms; Time Factors

We report the results of a therapeutic trial in patients with rectocolic and gastric metastatic adenocarcinomas. This trial is based on experimental evidence that an excess of reduced intracellular folic acid increases the cytotoxicity of fluoropyrimidines. The treatment consists of 5-fluorouracile (5-FU) (370 to 400 mg/m2/24 h) and folinic acid in high doses (200 mg/m2: 24 h) given simultaneously for 5 consecutive days; the interval between courses is 21 days. Thirty patients with measurable rectocolic adenocarcinomas were evaluated. They were divided into two groups: 16 patients had had no previous chemotherapy and 14 had not responded to chemotherapy with 5-FU alone or associated with other cytostatic drugs. Response rates were 56% in the first group and 21% in the second. Five patients with measurable gastric adenocarcinomas were also evaluated; none had received previous chemotherapy. A partial response was recorded in three of these patients. Toxicity of the therapeutic regimen was acceptable. Stomatitis was the most common toxic side-effect. In patients with severe adverse side-effects recurrence was efficiently prevented by decreasing the daily dose of 5-FU to 30 mg/m2 during subsequent courses. We conclude that in the tumors studied folinic acid in high doses can improve the antitumoral effect of 5-FU and induce a response to this agent in some rectocolic tumors which were previously resistant.

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Middle Aged; Pilot Projects; Rectal Neoplasms; Stomach Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Leukocyte Count; Male; Middle Aged; Pilot Projects; Platelet Count; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Arteries; Brain Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Catheterization; Chloramphenicol; Facial Neoplasms; Fever; Fluorouracil; Head and Neck Neoplasms; Humans; Infections; Infusions, Parenteral; Leucovorin; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Neoplasm Metastasis; Palliative Care; Penicillins; Stomach Neoplasms; Thoracic Neoplasms