levoleucovorin and Esophageal-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

Cystic fibrosis (CF) is a multisystem disease affecting the gastrointestinal (GI) tract as well as the lungs. As survival has increased significantly over the past few decades, complications not seen previously have become apparent. There is an overall increased rate of malignancy in CF, particularly from the GI tract and in the post-transplant population. The most common sites of malignancy are the pancreatico-biliary and digestive tract, as well as an increased rate of testicular cancer. Using an illustrative case of metastatic oesophageal malignancy which initially appeared to be hepatic in origin, we have reviewed the literature surrounding malignancy in CF with a particular focus on the GI tract.

Topics: Adenocarcinoma, Clear Cell; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cystic Fibrosis; Esophageal Neoplasms; Fatal Outcome; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds

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

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

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

Irinotecan (Camptosar) has shown activity in several solid tumor malignancies, including gastric and pancreatic cancer. In vitro studies suggest antitumor activity in esophageal cancer cell lines. Sequence-dependent synergy has been demonstrated in vitro between irinotecan and cisplatin. A phase I trial conducted at Memorial Sloan-Kettering Cancer Center (MSKCC) has demonstrated the safety and tolerability of cisplatin plus irinotecan. A phase II study of this combination in patients with previously untreated, advanced esophageal cancer, also at MSKCC, has demonstrated promising results. Current trials at MSKCC are attempting to combine this regimen with either paclitaxel (Taxol), fluorouracil (5-FU), or radiation therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Enzyme Inhibitors; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Paclitaxel; Topoisomerase I Inhibitors

Topics: Carcinoma, Squamous Cell; Circadian Rhythm; Cisplatin; Clinical Trials as Topic; Colorectal Neoplasms; Drug Administration Schedule; Esophageal Neoplasms; Floxuridine; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Interferons; Leucovorin

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

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

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

To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.. After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.. Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.. Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemoradiotherapy; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Survival Rate; Young Adult

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deglutition Disorders; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Palliative Care; Radiation Dose Hypofractionation; Treatment Outcome

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

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

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

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

The ongoing phase 2/3 PRODIGE 26/CONCORDE trial compares chemoradiation therapy with and without dose escalation in patients with locally advanced or unresectable esophageal cancer. The results of a benchmark case procedure are reported here to evaluate the protocol compliance of participating centers as part of quality assurance for radiation therapy.. Volume delineation, target coverage, and dose constraints to the organs at risk (OARs) were assessed on treatment plans of a common benchmark case performed by each participating center. The centers were classified in 3 categories: per protocol, minor acceptable deviation (MiD), or major unacceptable deviation (MaD). A plan was rejected if ≥4 MiDs or 1 MaD were found.. Thirty-5 centers submitted 43 plans. Among them, 14 (32.6%) were per protocol, 19 (44.2%) presented at least 1 MiD, 2 (4.6%) presented at least 1 MaD, and 8 (18.6%) presented both MiD and MaD. Overall, 11 (25.6%) plans were rejected. Only 1 plan was rejected because gross tumor volume was not correctly delineated. The OAR delineation was respected in all cases. Dose constraints to the OARs were respected in the majority of cases except for the heart, where one-third of the plans presented a deviation. As for the target volume, 3 plans (5.8%) had a major underdosage and 1 plan (1.9%) had a major overdosage. Overall, 58% of all treatments were planned with intensity modulated radiation therapy, whereas 42% were planned with 3-dimensional chemoradiation therapy. Significantly more plans in the intensity modulated radiation therapy group were accepted compared with the 3-dimensional chemoradiation therapy group (P = .03).. The high frequency of protocol deviations underlines the importance of a quality assurance program in clinical trials. Further work should assess the impact of quality assurance for radiation therapy on patient outcomes.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Benchmarking; Cancer Care Facilities; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; France; Guideline Adherence; Heart; Humans; Kidney; Leucovorin; Liver; Lung; Lymph Nodes; Lymphatic Irradiation; Male; Organoplatinum Compounds; Organs at Risk; Quality Assurance, Health Care; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Spinal Cord; Tumor Burden

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

A recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival.. A total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18).. Both groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil-cisplatin arm only (p = 0.047). During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil-cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020).. Analyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil-cisplatin regimen as part of definitive CRT.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Fluorouracil; France; Humans; Leucovorin; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Organoplatinum Compounds; Prospective Studies; Quality of Life; Risk Factors; Surveys and Questionnaires; Time Factors; 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 optimal perioperative treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. We evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapies administered adjuvantly for curatively-resected, node-positive ESCC.. Patients with pathologically node-positive esophageal cancer after curative R0 resection were enrolled and randomly assigned to receive LV5FU2 or FOLFOX biweekly for up to eight cycles. The primary endpoint was disease-free survival (DFS).. Between 2011 and 2015, 62 patients were randomized into the two treatment groups (32 in the LV5FU2 arm and 30 in the FOLFOX arm). The median age was 60 years and both groups had similar pathologic characteristics in tumor, nodal status, and location. Treatment completion rates were similarly high in both groups. The DFS rate at 12 months was 67% in the LV5FU2 group and 63% in the FOLFOX group with a hazard ratio of 1.3 (95% confidence interval [CI], 0.66 to 2.62). After a median follow-up period of 27 months, the median DFS was 29.6 months (95% CI, 4.9 to 54.2) in the LV5FU2 arm and 16.8 months (95% CI, 7.5 to 26.1) in the FOLFOX arm (p=0.428), respectively, while the median overall survival was not reached in either arm. Grade 3 or 4 neutropenia was more frequent in patients in the FOLFOX arm than the LV5FU2 arm (20.0% vs. 3.1%).. The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome

This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy.. A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients.. Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC.. We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Body Mass Index; Bone Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Models, Biological; Organoplatinum Compounds; Predictive Value of Tests; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; ROC Curve; Serum Albumin; Survival Rate; Treatment Outcome; Vinblastine; Vinorelbine

To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer.. Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected.. Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding.. Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Chemoradiotherapy; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; France; Humans; Kaplan-Meier Estimate; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Time Factors; Treatment Outcome

The role of preoperative chemotherapy in squamous cell esophageal carcinoma remains controversial. A prospective trial was initiated to investigate whether preoperative chemotherapy followed by surgery results in increased progression-free survival in patients with resectable thoracic esophageal carcinoma.. Patients with Stage IIb-IIIa/b resectable esophageal carcinoma were eligible for the study. They received two cycles of FLEP regimen chemotherapy (cisplatin, etoposide, leucovorine, 5-fluorouracil) followed by transthoracic extended 2- or 3-field esophagectomy. Two-year progression-free survival was the primary endpoint. To evaluate the potential benefit of the dual-modality approach we compared these results with the outcome of patients who were treated in our center in the same period of time and were non-randomly allocated to surgery alone.. From 2001 to 2008, 63 patients were included in the study (bimodality group) and 58 patients into the surgery-alone group. Median follow-up was 68 (range, 4-123) months. Squamous cell carcinoma had 93% patients. Two-year progression-free survival for all patients was 45.3 and 30.7% (hazard ratio 0.71, 95% confidence interval 0.46-1.08) and median overall survival was 26.5 months and 18.0 months (hazard ratio 0.67, 95% confidence interval 0.41-1.01) in bimodality- and surgery-alone groups, respectively. Patients who underwent R0-resection after bimodality treatment had significantly better overall survival (40.9 months) than after surgery alone (19.0 months, hazard ratio 0.51, 95% confidence interval 0.30-0.81).. Two cycles of preoperative chemotherapy did not improve progression-free survival of patients with resectable thoracic esophageal carcinoma in intent-to-treat population. However, significantly better results of bimodality approach was seen in R0-resected patients which warrants further trials with more effective chemotherapy combinations.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Prospective Studies

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

Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial.. PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio.. This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors.. NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Paclitaxel; Prospective Studies; Survival Analysis; Treatment Outcome; Young Adult

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

To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data.. Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma.. This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death.. In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Squamous Cell; Cetuximab; Cisplatin; Disease Progression; Disease-Free Survival; Epirubicin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Survival Rate; Time Factors; Treatment Failure

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 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

Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.. We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.. 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group.. Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery.. UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds

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

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

To evaluate the efficacy and toxicity of nedaplatin (NDP) concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma.. Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group (n = 34) or a cisplatin (DDP) group (n = 34). The NDP group received NDP 80-100 mg/m² iv on day 1 + leucovorin (CF) 100 mg/m² iv on days 1-5 + 5-fluorouracil (5-FU) 500 mg/m² iv on days 1-5. The DDP group received DDP 30 mg/m² iv on days 1-3 + CF 100 mg/m² on days 1-5 + 5-FU 500 mg/m² iv on days 1-5. The treatment was repeated every 4 wk in both groups. Concurrent radiotherapy [60-66 Gy/(30-33 f)/(6-7 wk)] was given during chemotherapy.. There was no significant difference in the short-term response rate between the NDP group and DDP group (90.9% vs 81.3%, P = 0.528). Although the 1- and 2-year survival rates were higher in the NDP group than in the DDP group (75.8% vs 68.8%, 57.6% vs 50.0%), the difference in the overall survival rate was not statistically significant between the two groups (P = 0.540). The incidences of nausea, vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group (17.6% vs 50.0%, P = 0.031; 11.8% vs 47.1%, P = 0.016; 8.8% vs 38.2%, P = 0.039). There was no significant difference in the incidence of myelosuppression, radiation-induced esophagitis or radiation-induced pneumonia between the two groups.. NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma. NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; China; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Radiotherapy Dosage; Radiotherapy, Conformal; Survival Rate; Time Factors; Treatment Outcome; Young Adult

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

We evaluated the feasibility and tolerability of triple- versus double-drug chemotherapy in elderly patients with oesophagogastric cancer.. Patients aged 65 years or older with locally advanced or metastatic oesophagogastric cancer were stratified and randomised to infusional 5-FU, leucovorin and oxaliplatin without (FLO) or with docetaxel 50 mg/m(2) (FLOT) every 2 weeks. The study is registered at ClinicalTrials.gov, identifier NCT00737373.. One hundred and forty three (FLO, 71; FLOT, 72) patients with a median age of 70 years were enrolled. The triple combination was associated with more treatment-related National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 adverse events (FLOT, 81.9%; FLO, 38.6%; P<.001) and more patients experiencing a ≥10-points deterioration of European Organization for Research and Treatment of Cancer Quality of Life (EORTC QoL) global health status scores (FLOT, 47.5%; FLO 20.5%; p=.011). The triple combination was associated with more alopecia (P<.001), neutropenia (P<.001), leukopenia (P<.001), diarrhoea (P=.006) and nausea (P=.029).). No differences were observed in treatment duration and discontinuation due to toxicity, cumulative doses or toxic deaths between arms. The triple combination improved response rates and progression-free survival in the locally advanced subgroup and in the subgroup of patients aged between 65 and 70 years but not in the metastatic group or in patients aged 70 years and older.. The triple-drug chemotherapy was feasible in elderly patients with oesophagogastric cancer. However, toxicity was significantly increased and QoL deteriorated in a relevant proportion of patients.. The study was partially funded by Sanofi-Aventis.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Feasibility Studies; Female; Follow-Up Studies; Humans; Leucovorin; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Quality of Life; Survival Rate; Taxoids

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

Squamous cell carcinoma is the main histological subtype of esophageal cancer in the east Asia. Oxaliplatin and fluorouracil are active agents for esophageal carcinoma. The aim of this phase II study was to evaluate the efficacy and safety of oxaliplatin, fluorouracil and leucovorin in patients with metastatic esophageal squamous cell carcinoma (ESCC).. Patients with metastatic ESCC and Eastern Cooperative Oncology Group performance score of 0-2 who had not received prior systemic chemotherapy for metastatic disease were enrolled. Oxaliplatin, 100 mg/m(2), was administered as a 2-h intravenous (i.v.) infusion on day 1. Leucovorin, 400 mg/m(2) i.v., was administered as a 2-h infusion followed by fluorouracil (400 mg/m(2)) i.v. bolus immediately followed by fluorouracil (2,400 mg/m(2)) as a 46-h continuous infusion on days 1 and 2. Chemotherapy was repeated every 14 days.. Between October 2008 and September 2011, fifty-six patients, with a median age of 59 years, were enrolled in this study. The overall response rate was 23.2 % with a disease control rate of 67.9 %. The median progression-free survival (PFS) was 4.4 months, and the median overall survival (OS) was 7.7 months. Median PFS was significantly longer in patients without liver metastasis than those with liver metastasis (5.4 vs 2.4 months, P = 0.003). Partial response was associated with longer PFS (7.2 vs 2.7 months, P = 0.023) and OS (11.3 vs 7.1 months, P = 0.028). Significant difference in OS was noted between those age >65 and ≤ 65 years of age (7.9 vs 3.3 months, P = 0.033). Grade 3/4 neutropenia, leucopenia, anemia and thrombocytopenia occurred in 35.7, 28.6, 10.7 and 10.7 % of patients, respectively. The most common non-hematologic toxicities were fatigue, mucositis, nausea/vomiting and peripheral neuropathy, all of which were moderate, reversible and did not require a dose reduction.. Chemotherapy with oxaliplatin, leucovorin and fluorouracil showed moderate antitumor activity in metastatic ESCC and was well tolerated with acceptable myelosuppression, infrequent and reversible non-hematologic toxicities in patients with ESCC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin

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

Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.. We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).. In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.. Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cetuximab; Combined Modality Therapy; Cytokines; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Intercellular Signaling Peptides and Proteins; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Positron-Emission Tomography; Predictive Value of Tests; Radiotherapy, Adjuvant

A complete pathologic response to neoadjuvant chemotherapy, without the use of radiation, has infrequently been reported in operable chemo-naïve stage III esophageal adenocarcinoma patients.. Twenty-nine eligible patients were enrolled in the study. Neoadjuvant therapy consisted of 5-fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel and was administered in two 4-week cycles. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathologic response were not offered any further chemotherapy.. Twenty-four out of 29 patients finished neoadjuvant therapy and underwent curative esophagectomy. Two patients were declared inoperable after treatment, and three patients died prior to surgery. The median follow-up on all patients was 20.2 months. Median progression-free survival and median overall survival were 13.6 and 21.4 months, respectively. Clinical response to neoadjuvant chemotherapy was seen in 21 out of 29 patients (72.4%). Complete pathologic response with neoadjuvant chemotherapy was seen in 4 out of 24 patients (16.7%). Those four patients have been alive and progression-free for 20-37 months. Grade 3-4 toxicities occurred in 16 of the 29 patients during neoadjuvant therapy. Grade 3-4 toxicities were seen in 6 out of 14 patients during adjuvant therapy. (18)F-fluorodeoxyglucose-positron emission tomography standardized uptake values of ≥8 correlated with better progression-free survival.. 5-Fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel regimen is active in patients with esophageal adenocarcinoma. Toxicity profiles are manageable. Neoadjuvant chemotherapy allowed achievement of complete pathologic response without radiation. (18)F-fluorodeoxyglucose-positron emission tomography standardized uptake values might be prognostic.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Docetaxel; Esophageal Neoplasms; Esophagectomy; Female; Floxuridine; Follow-Up Studies; Gastrectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Taxoids; Time Factors; Treatment Outcome

There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers.. Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways.. A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%).. In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease-Free Survival; Erlotinib Hydrochloride; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Protein Kinase Inhibitors; Quinazolines

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

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

Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil.. Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts.. A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively.. Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds

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 aim of this study was to evaluate the activity and safety of oxaliplatin/5-fluorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer.. Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m(2)), and leucovorin (20 mg/m(2) on days 1,8,15,29,36,43,50,57) followed by continuous infusion fluorouracil (200 mg/m(2) per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemo-radiotherapy completion. The primary endpoint was 1-year progression-free survival.. Forty (68%) patients completed treatment without modifications. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR. At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent.. Concurrent oxaliplatin, leucovorin, fluorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Radiation Dosage

In the majority of patients with oesophageal carcinoma, curative treatment proves to be impossible when diagnosis was established; therefore, most of the patients are candidates for palliative chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of 5-fluorouracil/folinic acid (AIO regimen) plus irinotecan in patients with locally advanced or metastatic carcinoma of the oesophagus. The methods used a prospective phase II trial, start: November 2002; patients: n=25; chemotherapy: irinotecan (80 mg/m2) as a 1-h infusion and 5-fluorouracil (2000 mg/m2) with sodium folinic acid (500 mg/m2) as a 24-h infusion on days 1, 8, 15, 22, 29 and 36, repeated on day 57. Last date of evaluation: 28 February 2007; n=24; adenocarcinoma: n=13, squamous cell carcinoma (SCC): n=11; UICC III/IV: 3/21; grading G1/G2/G3/G4: 0/8/12/4; median age: 58 years (range 44-75); men/women: 19/5; Eastern Cooperative Oncology Group index 0/1/2: 3/17/4; applications: 460. Higher-grade toxicity: grade 3 diarrhoea: n=2, grade 4 diarrhoea: n=1, grade 4 vomiting: n=1, grade 4 nausea: n=1, grade 3 fatigue: n=1, grade 3 hyponatraemia: n=2, grade 4 elevation of creatinine: n=1, thrombosis of the vena subclavia: n=1, ischaemic lesion of the brain stem: n=1. Three patients died after two chemotherapeutic applications because of high tumour burden. Evaluable for response: n=19. Partial response: n=8 (33%), stable disease: n=9 (38%), progressive disease: n=2 (8%), not evaluable: n=5 (21%). Time-to-progression: 6.6 months (range 1.6-24.6). Total median survival: 13.6 months (median survival of adenocarcinoma: 20.3 months, median survival of SCC: 10.0 months). Secondary resection (R0): n=3. In oesophageal carcinomas, the AIO regimen plus irinotecan is excellently manageable as an outpatient treatment and shows efficacy in adenocarcinomas and SCCs of the oesophagus.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Palliative Care; Prospective Studies; 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

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

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m(-2), bolus 5FU 300-400 mg/m(2), continuous infusion 5FU 400-600 mg m(-2) on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m(-2) on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m(-2), and continuous infusion 5FU was 600 mg m(-2) day(-) (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m(-2) and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin

Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer.. Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination of dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates.. Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response.. Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m2 Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Paclitaxel; Radiotherapy Dosage; Tegafur; Uracil

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

Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival.. Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m2 on Day 1 and 5-fluorouracil 350 mg/m2 and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy.. Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p < 0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%.. Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Esophagectomy; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Radiotherapy Dosage

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

A phase II trial to evaluate neoadjuvant (NAD), surgery and adjuvant (AD) combination chemotherapy without radiation therapy (RT) for patients with esophageal adenocarcinoma staged with endoscopic ultrasound and CT as T3N1 was carried out.. Thirty-three eligible patients were enrolled. NAD therapy was administered in two 49-day cycles and included cisplatin, floxuridine, paclitaxel and leucovorin. Esophageal resection was performed followed by AD therapy.. Thirty-three patients initiated NAD therapy; 10 experienced grade 3 and 4 toxicities, which included leucopenia, fatigue, nausea, diarrhea and stomatitis. Additionally, 16 patients experienced grade 1 and 2 hematologic and non-hematologic toxicities. Fifteen patients were down-staged, of whom five were T2, seven were T1, and three had nodal disease with no evidence of residual cancer in the esophageal bed. Fifteen patients remained T3, and two showed progressive disease. Thirty-two patients proceeded to surgery and 30 were resected. Although all resected patients were eligible for AD therapy, 15 did not receive it either because of patient refusal or surgeon recommendation. Fifteen patients received AD therapy: nine who had remained T3 and six who had down-staged. Three patients experienced grade 3 and 4 toxicities similar to those in NAD therapy. Six patients had grade 1 and 2 toxicities. Kaplan-Meier estimates of overall survival at 1, 3 and 5 years were 73% (95% CI: 58-88%), 52% (95% CI: 34-69%) and 29% (95% CI: 13-45%), respectively. Median survival was 42 months.. Deletion of RT may safely allow for more aggressive chemotherapy and increase chances of survival. The results need to be confirmed in a randomized phase II or larger phase III trial.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Female; Floxuridine; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Paclitaxel

This study assessed the clinical activity and safety of twice-weekly paclitaxel and cisplatin combined with 5-fluorouracil and leucovorin (TP-HDFL) in patients with recurrent or metastatic esophageal squamous cell carcinoma. The regimen, composed of paclitaxel 35 mg/m 1-h intravenous infusion on days 1, 4, 8 and 11; cisplatin 20 mg/m 2-h intravenous infusion on days 2, 5, 9 and 12; and 5-flourouracil 2000 mg/m and leucovorin 300 mg/m 24-h intravenous infusion on days 5 and 12; repeated every 21 days. Forty-one patients (median age 51), 15 with de-novo metastatic disease and 26 with recurrent disease, were enrolled. Grades 3-4 neutropenia, leukopenia and diarrhea occurred in 37.8, 29.4 and 14.2% of cycles, respectively. One patient died of invasive fungal infection. Three complete responses, 13 partial response and 13 stable diseases were observed. The intent-to-treat response rate was 39.0% (95% confidence interval: 24-54). The median progression-free and overall survival were 6.3 and 8.9 months (range 1-50+), respectively. Twice-weekly TP-HDFL has the activity and toxicity profile similar to the previously reported same three-drug combination for advanced esophageal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel

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

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

Combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin is regarded as the standard regimen for advanced esophageal carcinoma. This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens, based on platinum compound plus 5-fluorouracil in the treatment of advanced esophageal carcinoma, and to further explore prognostic factors of advanced esophageal carcinoma.. From October 1999 to December 2004, 98 patients with advanced esophageal carcinoma were enrolled in the study. They were non-randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m(2), followed by a 5-FU bolus 400 mg/m(2) and 48-hour infusion of 5-FU 3,000 mg/m(2) every 3 weeks, combined with cisplatin 80 mg/m(2) (DLF, n=48) or with carboplatin AUC=5 on day 1 (CLF, n=32), or with cisplatin 80 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1-5 plus pingyangmycin 5 mg/m(2) on day 1, 3, 5 (DFM, n=18). Survival analysis and prognostic factors were evaluated by Kaplan-Meier method and Cox regression analysis.. All 98 patients were assessable for response and toxicity. There were 13 complete response, 36 partial response, 45 no changes and 4 progressive disease with a total response rate of 46.86%. The response rates of DLF, CLF and DFM regimens were 60.42%,46.86% and 27.78%, respectively (DLF vs DFM, P=0.027). The major side effects were nausea-vomiting, alopecia, bone marrow suppression and mucositis, and the others were uncommon. All side effects were tolerable and mild except for nausea-vomiting. Nausea-vomiting was mildest in CLF among the three regimens. After a median follow-up of 9 months, the overall median survival was 9 months (95% CI, 6.67 to 11.33 months), the median survival of the patients treated with DLF, CLF or DFM regimen was 10, 9 and 7 months, respectively (P=0.7402). Better prognosis was correlated with good conditions of patients before chemotherapy (KPS> or =80, P=0.000) and metastasis to lymph node, parenchyma or bone in stead of visceral organs (P=0.026). There was no correlation between the prognosis and age, sex, types of pathology and the regimen of therapy.. The DLF regimen is tolerable and more effective, thus could be recommended as a front-line standard treatment for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble and older patients since it has the mildest side effects. The prognostic factors of advanced esophageal carcinoma include conditions before chemotherapy and the location of metastasis.

Topics: Adenocarcinoma; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Proportional Hazards Models; Remission Induction; Survival Rate

Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.. Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time.. The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001).. Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Survival Analysis

Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer.. Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy.. Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery.. The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Female; Humans; Leucovorin; Male; Middle Aged; Radiation-Sensitizing Agents; Tegafur; Uracil

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

The aim of this study was to evaluate the overall response rate, toxicity and overall survival in patients with locally advanced or metastatic esophageal cancer treated with gemcitabine, 5-fluorouracil (5-FU) and leucovorin.. Patients with either adenocarcinoma or squamous cell carcinoma of the esophagus could enroll; however, patients could not have received prior chemotherapy for metastatic disease. Treatment cycles consisted of infusions of all three agents at days 1, 8 and 15, repeated every 28 days. Patients received gemcitabine 1,000, leucovorin 25 and 5-FU 600 mg/m(2). Tumor assessment was performed every 2 cycles. Responses were assessed using the Eastern Cooperative Oncology Group solid tumor response criteria.. Thirty-five patients with metastatic or locally advanced esophageal cancer enrolled. One complete response and ten partial responses were observed for an overall response rate of 31.4%. An additional 11 patients had stable disease as their best response. The median survival was 9.8 months with a 1-year survival rate of 37.1%. Toxicity was predominately hematologic, with 58% of patients experiencing grade 3 or 4 neutropenia.. The combination of gemcitabine, 5-FU and leucovorin had activity in advanced esophageal cancer. Patients tolerated the regimen well, with myelosuppression occurring most commonly. The combination merits further investigation as a treatment for esophageal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Deoxycytidine; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Gemcitabine; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Survival Analysis; Treatment Outcome

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

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

The prognosis for advanced esophageal carcinoma is poor with a median survival of 9-12 months and 5-year-survival rate of 10-20%. Combination chemotherapy with cisplatin and 5-fluorouracil (5-FU) is considered to be the standard therapy, but has a high potential of side effects and is usually not given on an ambulatory basis. This phase I study was designed to find the maximum tolerated dose (MTD) of weekly cisplatin in combination with standard doses of gemcitabine (1,000 mg/m(2), 30 min) and 5-FU (750 mg/m(2), 24 h)/folinic acid (200 mg/m(2), 30 min). All drugs were to be given on a day 1, 8, 15 and 22 of a 6-weekly cycle in an outpatient setting. Nineteen chemonaive patients with inoperable stage IIa, III and IV squamous cell carcinoma and adenocarcinoma of the esophagus were enrolled into the study. Eight, six and five patients were enrolled at cisplatin dose levels 0 (20 mg/m(2) ), I (25 mg/m(2) ) and II (30 mg/m(2)), respectively. One hundred and eighty-one out of 187 treatments (55 cycles) were given on an outpatient basis. The dose-limiting toxicities of this schedule were leukopenia and thrombocytopenia. Other side effects were mild. Dose level II (30 mg/m(2)) was defined as the MTD for cisplatin when used in this combination and schedule. Partial responses were observed in 10 of the 19 enrolled patients. The side effect profile seen in this study in combination with the preliminary evidence of efficacy justifies further testing in a phase II setting with a cisplatin dose of 25 mg/m(2) and offers a treatment option for patients in an outpatient setting.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deoxycytidine; Esophageal Neoplasms; Female; Fluorouracil; Gemcitabine; Humans; Leucovorin; Male; Middle Aged

The objective of this study was to determine the toxicity and the efficacy of the combination of cisplatin, etoposide, 5-fluorouracil (5-FU) and folinic acid in the treatment of patients with advanced squamous cell carcinoma of the esophagus. Patients received cisplatin 80 mg/m(2) i.v. on day 1, etoposide 125 mg/m(2) i.v. on day 1 and etoposide 200 mg/m(2) p.o. on days 3 and 5, 5-FU 375 mg/m(2)/day continuously i.v. combined with folinic acid 30 mg p.o. 6 times per day on days 1--4. Courses were repeated every 4 weeks until progression or up to a maximum of 6 courses. Patients were evaluated for response after every two courses. Sixty-nine patients received a total of 291 courses (median 4, range 1--6). The hematological toxicity consisted of leukocytopenia grade 3 or 4 in 17 and 16% of patients, respectively. Leukocytopenic fever was seen in 19% of patients. Thrombocytopenia grade 3 or 4 was seen in 13 and 7% of patients, respectively. Non-hematological toxicity consisted of nausea/vomiting grade 3 in 32%, diarrhea grade 3 in 6% and mucositis grade 3 or 4 in 23% of patients. The overall response rate was 34% (complete response 4%, partial response 30%) and the median time to progression was 7 months in 13 patients who received no additional treatment. The median survival for all patients was 9.5 months with a 1-year survival rate of 36%. Ten patients with initially locally unresectable disease (N=2) or celiac or supraclavicular lymph node metastases (N=8) who received additional treatment (esophageal resection in seven patients and radiotherapy in three patients) after they had responded to chemotherapy had a 3-year survival of 50%. We conclude that the combination cisplatin and etoposide combined with 5-FU and folinic acid is a safe and active regimen for patients with advanced squamous cell carcinoma of the esophagus. Mucositis is the most prevalent toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged

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

The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates.. From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival.. Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 +/- 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834.. NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cost-Benefit Analysis; Drug Therapy; Epirubicin; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Radiotherapy Dosage; Survival Analysis; Tomography, X-Ray Computed

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Survival Rate; Treatment Outcome

In a multicenter phase II study, 30 patients with unresectable, locally advanced or metastatic squamous cell or adenocarcinoma of the esophagus were treated with folinic acid 200 mg/m2/d, 5-FU 300 mg/m2/d, and cisplatin 20 mg/m2/d intravenously for 5 days every 4 weeks. Two of 13 patients with squamous cell carcinoma (SCC) had a complete response (CR), but one died of pneumonia after 9 months while still in CR, and the other still in CR after more than 5 years. Six other patients (3 SCC, 2 of 16 with adenocarcinoma, 1 mixed histology) had a partial response with a median duration of 9 months (range 5 to 57 + months) for an overall response rate of 27%. A further 6 patients (20%) had stable disease. Grade 4 neutropenia occurred in 6 patients (20%), with 5 requiring antibiotics for associated fever. Other grade 4 toxicities were nausea and vomiting (1), anemia (1), and thrombocytopenia (1); there were three early deaths (emphysema, cardiac arrest, pulmonary embolism). This combination appears to be an active, convenient regimen for advanced esophageal cancer, resulting in prolonged remission and survival in some patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease Progression; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Ontario; Severity of Illness Index; Treatment Outcome

The aim of this study was to clarify whether preoperative chemotherapy caused adverse effects on the perioperative course of patients undergoing esophagectomy. A total of 42 esophageal cancer patients were entered into a randomized trial and were analyzed. Twenty-one patients were assigned to immediate surgery (Surgery Group). The other 21 received two 5-day courses of chemotherapy comprising cisplatin (70 mg/m2) on day 1, and fluorouracil (700 mg/m2) and leucovorin (20 mg/m2) on each of days 1 to 5 (chemotherapy group). Hospital mortality comprised of one patient (2.3%) who had undergone an operation in the beginning of this series at 21 days after chemotherapy. Thereafter, the interval between the chemotherapy and operation was prolonged, with the average being 35 +/- 7 days. Preoperatively, both the lymphocyte counts and serum albumin levels were not increased in the chemotherapy group of patients even though their body weights increased. In the chemotherapy group, the operation time and the blood loss were increased and, on the 1st postoperative day, the development of systemic inflammatory response syndrome was high but the level of C-reactive protein was low. The incidence of positive microbial cultures of sputum and/or wound discharge within 8 postoperative days was higher in the chemotherapy group (42.9%) than in the surgery group (4.8%). The host defense damage caused by chemotherapy may be prolonged and may show adverse effects in patients undergoing esophagectomy in the early postoperative period. Minimally, a 4-week interval between the completion of chemotherapy and operation is recommended for preventing surgical mortality related to the preoperative chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Leucovorin; Preoperative Care; Time Factors

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

To define the activity and toxicity of preoperative chemotherapy and postoperative concomitant chemoradiotherapy in patients with carcinoma of the esophagus, and to determine the effect on survival in patients treated with this approach.. Patients were treated with two 21-day cycles of induction chemotherapy with cisplatin 100 mg/m2 on day 1, 5-fluorouracil (5-FU) 800 mg/m2/day continuous infusion on days 1-5, and leucovorin 100 mg/m2 every four hours on days 1-5. Surgical resection was performed if feasible (and could also be performed prior to chemotherapy). Patients then received radiotherapy (50 to 60 Gy) every other week x five to six weeks, concomitantly with 5-FU 800 mg/m2 continuous infusion daily and hydroxyurea 1 g twice daily x five days.. Forty-six patients were treated. With a minimum follow-up of 58 months, the median survival for the entire group was 16 months; the median survivals for patients with squamous carcinoma and adenocarcinoma were 29 months and 12 months, respectively. Toxicities of induction chemotherapy were severe neutropenia and mucositis; there was one toxic death. Toxicities of concomitant chemoradiotherapy were neutropenia, mucositis and esophagitis. There were five cases of radiation pneumonitis, one fatal.. Induction chemotherapy and postoperative concomitant chemoradiotherapy can be added to surgical resection for carcinoma of the esophagus. Combined modality therapy, as reported here, produces long-term survival benefit, particularly in patients with squamous carcinoma. However, similar outcome results have been reported with less toxic and shorter treatment regimens as tested in randomized studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagus; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Radiotherapy Dosage; Remission Induction; Survival Rate; Treatment Outcome

The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC.. Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation.. Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively.. This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cause of Death; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Preoperative Care; Survival Analysis; Treatment Failure

Most patients with esophageal carcinoma present with locally advanced disease and a poor prognosis. Surgery or radiation provides palliation for locally advanced esophageal carcinoma. The role of neoadjuvant therapy remains to be defined. We administered neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, interferon-alpha, and cisplatin to 11 patients with locally advanced disease.. Eleven patients with squamous cell or adenocarcinoma of the esophagus were treated peroperatively with two to three cycles of combination chemotherapy. Nine patients underwent resection with curative intent.. Six patients received three cycles of chemotherapy, and five received two. Dose reduction was necessary for two patients. One patient achieved a pathologic complete response, histologically confirmed. Of the eleven patients, two did not undergo surgery because of progressive disease during chemotherapy. Seven of the 9 patients relapsed after surgery and 2 have been disease free for 27 months.. The combination 5-FU leucovorin, interferon-alpha-2a, and cisplatin administered in a neoadjuvant setting resulted in a median survival of 11.8 months with a median time to relapse of 7 months.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Humans; Immunotherapy; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Recombinant Proteins; Survival Analysis

From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma; Cisplatin; Combined Modality Therapy; Disease Progression; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycins; Radiotherapy; Remission Induction; Survival Analysis

Cisplatin (P) and 5-fluorouracil (5FU) have demonstrated activity for the treatment of squamous cell carcinoma of the esophagus. Previous studies have shown that leucovorin (L) may potentiate the antitumoral activity of 5FU, so we tested the combination P-5FU-L in 31 patients with inoperable squamous cell esophageal carcinoma. Chemotherapy consisted of P 20 mg/m2 in 4 h, followed by L 200 mg/m2 in 2 h and 5FU 600 mg/m2 in 18 h. This schedule was repeated for 5 days every 4 weeks. The treatment plan included three courses of chemotherapy followed by radiotherapy. The overall response rate was 58% (95% CI = 39-76%), with one complete remission (3%), and 61% of patients reported an improvement in dysphagia. Gastrointestinal toxicity was the main side effect: grade 3-4 mucositis appeared in 19% of patients, grade 3-4 nausea/vomiting in 13%, and grade 3-4 diarrhea in 6.5%. There was one toxic death caused by neutropenia and sepsis. Nineteen patients received local radiotherapy after chemotherapy, which increased the overall response rate to 63% (5% complete responses). Dysphagia improved in 75% of them. The median survival for all patients was 11 months. This study shows that sequential therapy with P-5FU-L and radiotherapy achieves a high response rate as well as adequate symptomatic relief in patients with inoperable esophageal cancer. The results justify further evaluation of P-5FU-L in patients with earlier-stage disease.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Diarrhea; Drug Administration Schedule; Drug Synergism; Enzyme Inhibitors; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucous Membrane; Nausea; Radiotherapy, Adjuvant; Remission Induction; Survival Rate; Thymidylate Synthase; Vomiting

Eighteen patients with invasive periadventitial tissue (T4) or distant lymph node metastatic (M1,LYM) squamous cell carcinoma were entered into a pilot study of neoadjuvant chemotherapy with etoposide (50 mg/m2/day, days 1-5), leucovorin (30 mg/body/day, days 2-5), 5-fluorouracil (5-FU; 400 mg/m2/day, days 2-5) and cisplatin (100 mg/m2/day, day 1) (ELFP). The overall response rate was 56%. The response rates in the T4 tumor and M1,LYM patients were 56 and 50%, respectively. Radical esophagectomies were performed on six of 17 patients who had completely recovered from the chemotherapy, a resectability of 35%. Histologically, the primary tumor was moderately to slightly effective, and the lymph nodes markedly to moderately effective. Histologic responses in the lymph nodes were different from those in the primary tumors and in each node. There were four chemo-surgically related deaths. Median survival times in responding and non-responding patients were nine and three months, respectively. In conclusion, neoadjuvant chemotherapy with ELFP appears to be effective against esophageal squamous cell cancer with periadventitial tissue invasion or distant lymph node metastasis. Chemo-surgically related deaths were however, 22%, showing neoadjuvant chemotherapy to necessitate extremely careful attention to the medical and surgical management of patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Esophagectomy; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Pilot Projects; Survival Rate

We compared the clinical and pathological effects of preoperative combination chemotherapy using CDDP, 5-FU, and response rate for the primary lesion, an 81.8% response rate for intramural metastasis, 100.0% for intraepitherial spread, and a low response rate of 40.7% for lymph node metastasis. Pathological examination showed a 55.2% response rate for the primary lesion. There were seven cases in which the clinical assessment indicated that treatment was effective and pathological examination showed that it was ineffective, and three cases in which pathological examination showed a better response than clinical assessment. Cases showing a better clinical response included in which necrotic cancer lesion had disappeared due to absorption by the time of pathological examination, those with tumor regrowth after preoperative evaluation, those evaluated as showing a poor response due to residual cancer at the margin. Cases showing a better pathological response included those having remaining necrotic tissues and those having myoma beneath tumor. For intramural metastatic lesions, the pathological response rate was 42.9%, being lower than the clinical response rate. Metastasis to 209 lymph nodes showed a 23.0% response rate, with the abdominal nodes showing a poor response in comparison with those of the cervix and mediastinum. In 26 patients receiving preoperative radiotherapy, there was a significantly higher frequency of such changes as fibrous scar tissue, foreign body giant cells, vacuolation of tumor cells, and hyaloid degeneration of the lesion in comparison with the group receiving chemotherapy. Another difference was that the radiotherapy group showed a higher response of tumors with venous and lymphatic involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Preoperative Care

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Remission Induction; Thrombocytopenia; Treatment Outcome

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

Thirty-five patients with advanced epidermoid carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin 20 mg/m2, day 1-5 every 28 days. Six patients had a partial response (95% confidence limit, 7-35%) with a median response duration of 32 weeks. The median survival time of the patients on study was 14 weeks. The toxicity was acceptable, with only two patients experiencing severe hematologic toxicity and one patient experiencing severe nausea and vomiting. The addition of leucovorin at this dose level in this population of patients with advanced disease does not appear to enhance the activity of 5-FU for patients with squamous cell cancer of the esophagus. Since only a small percentage of patients experienced significant toxicity, a higher response rate could be achieved in patients treated with the maximally tolerated dose.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Evaluation; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Remission Induction; Survival Analysis

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

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

BACKGROUND Cisplatin/5-fluorouracil therapy is the standard therapy for unresectable and recurrent esophageal cancer. Cisplatin-based chemotherapy often causes adverse effects, such as nausea, vomiting, and renal dysfunction, which may necessitate dose modification or treatment prolongation. Therefore, novel combination therapies are urgently needed to improve the efficacy and overcome drug toxicity in this setting. CASE REPORT A 77-year-old man with advanced esophageal cancer received cisplatin/5-fluorouracil therapy as neoadjuvant chemotherapy. On day 8 of administration, the patient had lightheadedness, diaphoresis, and nausea and became unconscious and developed severe hyponatremia. We diagnosed the patient with cisplatin-induced syndrome of inadequate antidiuretic hormone secretion (SIADH). Subsequently, water restriction was started, and treatment with a salt-added diet and 3% hypertonic saline infusion was initiated. The hyponatremia improved and the patient was discharged on day 16 of administration. Therefore, neoadjuvant chemotherapy was discontinued, and surgical treatment was performed. However, the tumor recurred and chemotherapy was required. The patient developed severe hyponatremia while receiving neoadjuvant chemotherapy; hence, folinic acid, fluorouracil, and oxaliplatin therapy (FOLFOX) were administered as an alternative treatment. The patient completed the FOLFOX therapy without developing SIADH. CONCLUSIONS The cisplatin/5-fluorouracil therapy is currently the standard chemotherapy regimen for esophageal cancer. However, SIADH is a known adverse effect when using cisplatin. In patients with esophageal cancer, oxaliplatin appears to have a lower risk of SIADH than cisplatin, suggesting that oxaliplatin can be a therapeutic option for patients with esophageal cancer who are at high risk of SIADH.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Fluorouracil; Humans; Inappropriate ADH Syndrome; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Vasopressins

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

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

Oesophageal cancer is categorised among the most fatal cancers across the world with a mortality ranking of sixth position. Chemotherapy with FOLFOX-a regimen of fluorouracil, leucovorin, and oxaliplatin-has been approved in the treatment of oesophageal cancer owing to its lower toxicity compared with the previous regimens. We report the first case of a patient with oesophageal cancer metastatic to the hyoid presenting with sudden-onset shortness of breath and anterior neck swelling secondary to treatment with FOLFOX-6. CT was notable for subglottic soft-tissue swelling and cystic necrosis of the hyoid bone tumour, and the patient subsequently required placement of a definitive airway via tracheostomy. This case illustrates the importance of anticipating the need for pre-emptive tracheostomy in patients with hyoid bone tumours receiving treatment with FOLFOX.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Treatment Outcome

The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT).. All consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis.. A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54-66) and 48Gy (44.8-56) delivered in 30 (27-35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3-31.3) with a median V40 of 3.3% (0.0-25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9-4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%).. We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Disease-Free Survival; Dose Fractionation, Radiation; Esophageal Neoplasms; Esophageal Stenosis; Female; Fluorouracil; Heart; Humans; Leucovorin; Lung; Male; Middle Aged; Organoplatinum Compounds; Organs at Risk; Radiation Tolerance; Radiotherapy, Intensity-Modulated; Retrospective Studies; Time Factors; Treatment Outcome

Esophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach.. Demographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate.. Data for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p = 0.807), including major complications (24.0% vs. 23.6%, p = 0.943) and anastomotic leak (7.8% vs. 5.6%, p = 0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p = 0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p = 0.006. There was no difference between groups for overall or disease-free survival.. This study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are still lacking.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Disease-Free Survival; Docetaxel; Epirubicin; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Hospital Mortality; Humans; Length of Stay; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Postoperative Complications; Propensity Score; Survival Rate; Treatment Outcome

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

Topics: Adenocarcinoma; Capecitabine; Cisplatin; Docetaxel; Epirubicin; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Oxaliplatin

5-fluorouracil (5-FU) and cisplatin (CDDP) are common chemotherapy drugs used in the treatment of patients with advanced esophageal cancer. We investigated the efficacy of adding a continuous infusion of a large dose of a common adjuvant, citrovorumfactor (CF), to the traditional 5-FU/wCDDP regimen. 50 patients with advanced esophageal cancer were treated with a continuous infusion of CF, 5-FU, and CDDP, and the short-term effects, adverse reactions, and survival periods after treatment were analyzed. Overall, the treatment was effective in 58% of patients, and the therapeutic effects of the first-line of chemotherapy were significantly better than the second-line (u = 4.121, p < 0.05). Patients experienced severe nausea and vomiting in 18.7% of the treatment cycles and experienced severe hair loss or leucopenia in 1.9% of the treatment cycles. The majority of the treatment cycles produced only mild side effects. The median survival period following chemotherapy treatment was 10.6 months (95% confidence interval was 8.146 ~ 13.054 months), with the median survival time of patients with a Karnofsky Performance Status (KPS) score ≥ 80 being significantly longer than that of patients with KPS scores < 80 (χ

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chi-Square Distribution; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Karnofsky Performance Status; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome

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

AFP-producing adenocarcinoma of the esophagus and esophagogastric junction are rare tumor diseases. These tumors show an aggressive behavior characterized by early occurrence of liver metastases and mimic hepatocellular carcinoma (HCC). A general recommendation for palliative therapy is not established for these special tumors.Here we report about a 61-year-old man with multiple liver metastases and high serum alpha-fetoprotein (AFP) level. First, HCC was suspected, but further evaluation showed an AFP-producing adenocarcinoma of the esophagogastric junction with unusual findings on further immunohistochemical analysis. Palliative chemotherapy with FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) regime showed a 9 month duration of partial response.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Taxoids; Treatment Outcome

Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding.. Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding.. Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy.. Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deglutition Disorders; Docetaxel; Enteral Nutrition; Epirubicin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Quality of Life; Taxoids

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

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

We aimed to investigate the efficacy of second line treatment with modified FOLFOX6 (mFOLFOX6) following cisplatin- plus 5-fluorourasil (CF) chemotherapy in patients with metastatic esophagus cancer (mEC).. In our oncology clinic, between March 2011 and September 2014, we reviewed patients admitted with progressive mEC following first line CF chemotherapy and those with >60 kanofsky performance status performed second line mFOLFOX6 regimen.. A total of 242 patients with mEC were evaluated. 94 of 242 patients (38.8%) had received second-line chemotherapy treatment. All of these patients had received mFOLFOX6 regime. Median age was 53 years (range: 28-71). The received median number of chemotherapy cycles was 6 (2-12). Objective response rate (ORR) was obtained in 39 of 94 (41.4%) patients, 6 (6.3%) of these had complete response (CR) and 33 (35.1%) had partial response (PR). Stable disease (SD) was obtained in 20 (21.3%) patients and progression was observed in 35 (37.3%) patients. Grade ¾ toxicity was observed in 67 (71.2%) patients. The hematologic toxicity was found as the most common toxicity (69.1%).. mFOLFOX6 regimen as a second line treatment can be applied to the mEC patients with progressive disease following CF chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Squamous Cell; Cohort Studies; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Treatment Outcome

To compare chemotherapy first (group 1) versus self-expanding metal stent first (group 2) for the management of malignant dysphagia in unresectable oesophageal or gastro-oesophageal junction cancer.. Patients from two university hospitals with severe malignant dysphagia (dysphagia score ≥ 2) uneligible for surgery or radiochemotherapy were evaluated retrospectively.. Forty-two patients were included in group 1, and 29 in group 2. After 4 weeks, dysphagia scores improved by at least 1 point in 67% of patients in group 1 versus 93% in group 2 (p=0.01); 48% of patients in group 1 were able to eat solid food versus 68% in group 2 (p=0.054). In group 1, a self-expanding metal stent was secondarily placed in 18 patients (42.9%), whereas in group 2 dysphagia required a second self-expanding metal stent placement in 33.3% of patients.. Chemotherapy as the first treatment may be a valid option, avoiding self-expanding metal stent insertion in half of the patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophageal Stenosis; Esophagogastric Junction; Esophagoscopy; Female; Fluorouracil; Gastroscopy; Humans; Leucovorin; Male; Metals; Middle Aged; Organoplatinum Compounds; Palliative Care; Quality of Life; Retrospective Studies; Severity of Illness Index; Stents

Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis.. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation.. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases.. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Candidiasis; Endoscopy; Esophageal Neoplasms; Fluorouracil; Hematoporphyrins; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Photochemotherapy; Photosensitizing Agents; Treatment Outcome

Development of a second primary malignancy after an index esophageal cancer is a rare event, primarily due to short survival of patients with esophageal cancer. However, the number of long-term esophageal cancer survivors has been increasing due to advances in early detection and therapy.. We report herein a case of pancreatic adenocarcinoma that developed three years after a successfully treated early-stage adenocarcinoma of the esophagus. A 70-year-old Caucasian male presented with vague complaints of nausea, vomiting and abdominal distention, with subsequent development of jaundice. A computed tomography scan of abdomen revealed a 2.9 cm soft tissue mass in the head of the pancreas and the patient underwent a Whipple's procedure, with pathology confirming the diagnosis of pancreatic adenocarcinoma. Three years previously, the patient was successfully treated for adenocarcinoma of the esophagus via minimally invasive esophagogastrectomy. Despite chemoradiotherapy for localized disease and subsequent systemic chemotherapy for metastatic pancreatic cancer, the patient eventually succumbed to his illness.. We discuss the association between esophageal cancer and subsequent second malignancies, along with implications for surveillance and therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cholangitis; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Fatal Outcome; Fluorouracil; Gastrectomy; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Pancreaticoduodenectomy; Sepsis

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

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival. In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance. EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Resistance, Neoplasm; ErbB Receptors; Esophageal Neoplasms; Fluorouracil; Gene Dosage; Humans; Immunohistochemistry; Leucovorin; Neoadjuvant Therapy; Prognosis; Survival Analysis

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

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Central Venous Catheters; Esophageal Neoplasms; Extravasation of Diagnostic and Therapeutic Materials; Fluorouracil; Humans; Iatrogenic Disease; Leucovorin; Male; Mediastinitis; Mediastinum; Organoplatinum Compounds; Oxaliplatin

Cervical oesophagus represents a critical location for squamous cell carcinoma, which usually requires extensive surgery (pharyngo-laryngo-oesophagectomy). In the last decade, neoadjuvant chemo-radiotherapy was reported to be beneficial in the treatment of locally advanced squamous cell oesophageal cancer.. Between November 1997 and January 2012, 55 patients with locally advanced (T3-4) squamous cell oesophageal cancer received preoperative chemo-radiotherapy, where the tumour was localized in the upper third. Patients received preoperative irradiation of 3960 cGy in 180 cGy fractions and simultaneously Cisplatin and 5-FU chemotherapy. Restaging was carried out after four weeks and patients considered operable were underwent surgery.. In patients with cervical oesophageal cancer 35 of 55 (64%) underwent oesophageal resection or pharyngo-laryngectomy. In 16 out of 35 resected specimens (46%) complete histopathological remission (pCR) was observed. Perioperative mortality and anastomotic leaks were the same: 5/35 (14%). R0 resection rate was 82% and the 2- and 5 years survival rates were 41% and 18%. In 19 cases a larynx preserving pharyngo-oesophagectomy was performed and a free jejunal graft was used for reconstruction after a pharyngo-laryngectomy in 11 cases.. The high rate of pCR (46%) confirmed that upper third oesophageal cancer has superior sensitivity to multimodal treatment. In 30 cases neoadjuvant chemo-radiotherapy was able to achieve tumour regression and render pharyngo-laryngo-oesophagectomy unnecessary.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Dose Fractionation, Radiation; Drug Administration Schedule; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Laryngectomy; Length of Stay; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Pharyngectomy; Radiotherapy, Adjuvant; Treatment Outcome

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

Several studies have proven an ameliorated prognosis after a neoadjuvant therapy for locally advanced Barrett's carcinoma in case of response. The necessary amount of neoadjuvant chemotherapy within a multimodal therapy concept with following oesophageal resection has never been evaluated so far.. The clinical course of 122 patients with Barrett's carcinoma, who all underwent a neoadjuvant chemotherapy with cisplatin, five fluorouracil and leucovorin and following oesophagectomy, was reviewed. The pretherapeutic clinical and postoperative histopathological staging, histopathological response, clinical course, recurrence rates and long-term survival were retrospectively analysed and compared to the data of 30 patients, who were included in the same multimodal therapy concept, but who had to cease the chemotherapy early because of toxicity.. Postoperative pathological staging showed that the response rate correlates with the N and R status. The responding patients benefit from longer survival. Comparing the two subgroups, we could not find a significant difference in response rate, tumour staging, resection rate, long-term survival or pattern of recurrent disease. However, postoperative morbidity and mortality did not correlate with severe chemotherapy-induced toxicity.. This is the first study on the necessary number of chemotherapy cycles in terms of a neoadjuvant therapy for Barrett's carcinoma. We could show a similar downstaging effect, a good histopathological response and a comparable ameliorated long-term survival of patients with one compared to patients with three chemotherapy cycles. A biological selection seems to determine the course of the disease already at this early stage.

Topics: Aged; Antineoplastic Agents; Barrett Esophagus; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Cohort Studies; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Survival Rate; Treatment Outcome; Vitamin B Complex

To assess feasibility and tolerance of a modification in the usual radiochemotherapy regimen for esophageal cancer by using a leucovorin, 5-fluorouracil bolus, and infusion-cisplatin regimen (six cycles), beginning with two cycles of chemotherapy before conventional radiotherapy (50 Gy), 33 patients, 30 were men, 62.8 +/- 9.5 years, were treated for an esophageal carcinoma (29 squamous cell), 27 of these were in stage III (based on computed tomography scan). Neoadjuvant chemotherapy was well tolerated; concomitant radiochemotherapy was associated with severe adverse events mostly hematological in 23 patients. Complete response was achieved in 70%; median overall survival was 14 months, and 2-year survival was 40 +/- 11%. More than one-third of cycles could be performed as outpatients. This regimen seems safe and efficient, and could be conducted in an outpatient basis.

Topics: Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Pilot Projects; Vitamin B Complex

Chemotherapy-associated mucositis often prevents completion of an entire chemotherapy cycle. The underlying pathophysiology of chemotherapy-associated mucositis has not been well established. The individual immunologic predisposition of patients seems to play an important role.. One hundred fifty-six patients with locally advanced or metastatic esophageal adenocarcinoma received neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin followed by resection. Before the neoadjuvant therapy, monocytes were isolated from blood samples and were stimulated with lipopolysaccharide and interferon. An enzyme-linked immunosorbent assay was used to measure interleukin (IL)-10 and -12 levels and correlated with patients' clinical course.. Twenty-two patients (14,1%) developed grade III to IV mucositis (according to the NCI-Common toxicity criteria scales) within the neoadjuvant chemotherapy. Pretherapeutic low IL-10 (<24.1 pg/ml) and high IL-12 (>5500 pg/ml) levels were significantly associated with mucositis causing a therapy interruption or even cessation. Patients with high IL-10 (>43.6 pg/ml) and low IL-12 (<4408.5 pg/ml) levels had an uneventful neoadjuvant chemotherapy.. Pretherapeutic individual monocyte function is correlated with the development and the grade of chemotherapy induced mucositis. This knowledge might help us in predicting the grade of mucositis and in understanding the genesis regarding the association to pro- and anti-inflammatory effects of monocyte cytokines.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Fluorouracil; Humans; Interleukin-10; Interleukin-12; Leucovorin; Male; Middle Aged; Mucositis; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Prospective Studies; Survival Rate

The standard chemotherapy regimen for esophageal cancer is cisplatin and 5-fluorouracil (5-FU). We herein report a case of esophageal cancer associated with colon cancer, which was treated with combination chemotherapy of FOLFOX. The patient received chemotherapy of modified FOLFOX6 (mFOLFOX6) at dosages of 80% of standard regimen (oxaliplatin 68 mg/m2, levofolinate calcium 160 mg/m2, bolus 5-FU 320 mg/m2, and followed by continuous 5-FU 1,920 mg/m2/ 46 hr) in combination with radiotherapy (total 61.6 Gy). He developed grade 3 leukopenia after 2 courses of mFOLFOX6 and the 3rd course was started at dosages of 70% of standard regimen with 1 week delay. After that, no other adverse event without grade 2 esophagitis was appeared. Esophagogram revealed a partial response in primary tumor of the esophagus after 3 courses of chemotherapy with radiotherapy and blood chemistry examination showed negative squamous cell carcinoma antigen. One month after chemoradiotherapy, esophagogram revealed tracheoesophageal fistula, but tumor of the esophagus was well controlled. FOLFOX regimen combined with radiotherapy is well tolerated and effective for inoperable esophageal cancer. FOLFOX cannot be used for esophageal cancer in Japan, so clinical trial of FOLFOX for esophageal cancer should be conducted in the near future in Japan.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasms, Multiple Primary; Organoplatinum Compounds

Patients with advanced head and neck (H/N) and esophageal squamous cell carcinoma (SCC) often have a poor performance status and a dire prognosis. Our aim was to evaluate the feasibility, activity and quality of life (QOL) of an outpatient chemotherapy regimen consisting of cisplatin, 5-fluorouracil and leucovorin (CFL).. Prospective phase II study conducted at a Brazilian public institution.. Fifteen patients with residual, recurrent or metastatic SCC of the H/N or esophagus received bolus infusions of leucovorin 20 mg/m(2)/day and 5-fluorouracil 370 mg/m(2)/day on days 1-4, and 90 minutes of infusion of cisplatin 25 mg/m(2)/day on days 1-3, every 21 to 28 days, depending on hematological recovery. We also evaluated QOL by applying the European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC QLQ-C30) before each cycle.. The overall response rate was 36%, and the mean overall survival and progression-free survival were six and three months, respectively. We observed grade 3 or higher hematological toxicity in seven patients and one patient had grade 3 nausea and vomiting. One patient died because of neutropenic fever. Seven out of the 12 patients who could be evaluated regarding QOL presented an improvement in their overall health status and functional QOL scores over the course of the treatment.. CFL is an active outpatient protocol with tolerable toxicity and a favorable QOL impact. Larger studies are warranted, in order to confirm these results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Cost-Benefit Analysis; Epidemiologic Methods; Esophageal Neoplasms; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Outpatients; Quality of Life; Young Adult

It is still controversial whether adjuvant chemotherapy of cisplatin, 5-fluorouracil and leucovorin can increase the overall survival of esophageal cancer patients, and which subgroup of patients get most benefits from it. Between 1998 and 2004, 66 esophageal cancer patients with adjuvant chemotherapy and 160 well-matched patients without chemotherapy were included in this study. Nine markers were measured in the protein level to analyze prognostic significance. In the whole group, adjuvant chemotherapy did not improve the survival of esophageal cancer patients. There was also no significant difference for survival in stage I (P=0.59 and P=0.59), stage II (P=0.28 and P=0.28) and stage III patients (P=0.144 and P=0.06) between the observation and the chemotherapy group. Chemotherapy was most effective for the patients who had metastases in cervical and/or celiac lymph nodes (IV subgroup). One and 3-year disease-free survival and overall survival were significantly better than for those who did not receive the chemotherapy(P=0.038, and 0.016, respectively). Bcl-2 expression was a bad prognostic factor, and was more predictive in the adjuvant chemotherapy group than in the no-chemotherapy group. Adjuvant chemotherapy significantly improved the treatment result of stage IV patients compared with the observation group. Bcl-2 could be used to analyze prognosis and guide the adjuvant treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; China; Cisplatin; Cohort Studies; Disease-Free Survival; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged

The purpose of treatment in patients with advanced and metastatic esophageal cancer is to improve symptoms and maintain quality of life. Recently, the regimen including epirubicin, cisplatin, and 5-FU (ECF) has been used with protracted venous infusion (PVI), and has been reported to be an effective treatment for advanced and metastatic esophagogastric cancer. However, complications and the inconvenience associated with PVI cannot be justified for the treatment of advanced esophageal cancer. Therefore, we provided treatment with oral UFT and leucovorin instead of 5-FU PVI to improve convenience and catheter related complications.. Thirty-seven patients with advanced esophageal cancer were admitted between March 2002 and April 2005. The treatment schedule was as follows: epirubicin 50 mg/m2 iv on d 1, cisplatin 60 mg/m2 iv on d 1, oral UFT 300 mg/m2 and leucovorin 75 mg for 21 consecutive days of treatment followed by a 7-d treatment-free interval.. The response rate was 45.9% including one complete response (95% CI: 29.8%-62%). The median survival was 13 mo (95% CI: 10-16 mo). Four patients had adenocarcinoma. Interestingly, their response rate was 75% including one complete response. Myelosuppression was the most important toxicity. Other toxicities were tolerable.. The combination of epirubicin, cisplatin, UFT, and leucovorin (EPUL) could be another alternative to ECF in patients with advanced esophageal cancer. And this treatment might be more effective in adenocarcinoma of esophageal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Epirubicin; Esophageal Neoplasms; Female; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Prognosis; Survival Rate; Tegafur; Treatment Outcome; Uracil

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 role of endoscopic ultrasound (EUS) to evaluate treatment response postneoadjuvant therapy for restaging esophageal cancer prior to surgical resection is uncertain. Accuracy of EUS is lower but potential to predict response to chemoradiation indicates that EUS may be helpful prior to surgery.. To determine staging accuracy of EUS after neoadjuvant chemotherapy, predictors of tumor response, and survival in locally advanced esophageal cancer.. Single-center retrospective evaluation of patients with locally advanced esophageal cancer on a prospective chemotherapy study. Patients who underwent EUS without FNA pre- and postchemotherapy were included.. A total of 49 patients (43 men and 6 women) were evaluated with EUS pre- and postneoadjuvant chemotherapy. Forty-seven patients had tumor localized at the GE junction and two had mid-esophageal lesions. The median survival time was 53 months. Tumor and nodal staging accuracy postchemotherapy were 60% (27 of 45). T-stage accuracy postchemotherapy was superior in patients without a response to chemotherapy (95.7%vs 26.1%, p<0.0001). More than 50% in reduction of tumor thickness postchemotherapy was associated with tumor downstage and better survival. N0 disease on final pathology was the best predictor of improved survival.. Accuracy of EUS postchemotherapy is lower than initial staging accuracy; therefore the ability to predict downstaging based on EUS is marginal. Pathology N1 disease postchemotherapy is the best predictor of survival. EUS staging postneoadjuvant chemotherapy should focus on improving nodal staging accuracy with FNA.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Endosonography; Esophageal Neoplasms; Female; Floxuridine; Humans; Leucovorin; Lymph Nodes; Male; Neoadjuvant Therapy; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Taxoids

The frequently used chemotherapeutic drug 5-fluorouracil (5-FU) is known to cause angina pectoris and arrhythmias; myocardial infarction and sudden cardiac death could occur. Potential reasons for these phenomena range from toxic/metabolic disturbances to coronary artery spasms. This report shows angiographically proven spasmophilia of the coronary arteries and contributes to the understanding of angina pectoris occurring during treatment with 5-FU. Thus, verapamil type calcium antagonists as well as nitrates should be administered primarily in patients with coronary artery disease and in all patients who had been symptomatic during 5-FU administration in order to prevent further episodes.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Coronary Angiography; Coronary Circulation; Coronary Vasospasm; Electrocardiography; Esophageal Neoplasms; Esophagectomy; Exercise Test; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Regional Blood Flow

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

To date, only few reports are available on patients with esophageal carcinoma containing a tracheoesophageal fistula under chemotherapy.. A 56-year-old patient presented to the hospital with a stenosing squamous cell carcinoma of the esophagus containing a tracheoesophageal fistula 3 cm above the carina. After placement of a Port-a-Cath and adequate hydration he received weekly 500 mg/m (2) i. v. folinic acid (FA) as a 1 - 2-hour infusion and 2000 mg/m (2) 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) (AIO regimen) with prior application of bi-weekly 50 mg/m (2) i. v. cisplatin. A tracheal Y-Dumont metallic stent was inserted prior to initiating systemic treatment. The patient's alimentation was completely parenteral. After three cycles of chemotherapy (six months) the patient revealed complete remission (CR) with closure of the tracheoesophageal fistula. The tracheal Y-Dumont stent could be removed and the patient had oral alimentation restored. 29 months after initiating treatment he is without evidence of disease.. Patients with esophageal carcinoma containing a tracheoesophageal fistula might benefit from chemotherapy and should not be generally excluded from systemic treatment.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Remission Induction; Survivors; Tracheoesophageal Fistula; Treatment Outcome

There is rising evidence that anemia and blood transfusion increase perioperative mortality in cancer patients. Patients who are treated with neoadjuvant chemotherapy with a curative intent are exposed to toxicity that may negatively affect their future outcome.. The charts of 29 patients (21 males; median age, 59.5 years; range, 37 to 73), receiving neoadjuvant chemotherapy for cT3 esophagogastric adenocarcinoma operated at a single university center in the year 2002, were retrospectively reviewed to assess the incidence of anemia and blood transfusions.. Twenty-six patients received platinum-based chemotherapy over a period of 12 weeks and three patients more than 6 weeks. The median hemoglobin level (Hb level) before chemotherapy was 14.0 g/dL (range, 10.4 to 15.9 g/dL), the median decline of the Hb level was 2.9 g/dL (range, 0.3 to 6.3 g/dL); this drop was statistically significant (p < 0.001, 95% confidence interval). Patients who received preoperative blood transfusions (n = 8, 28%) had a significantly increased risk of developing postoperative complications (p = 0.028).. Preoperative chemotherapy for locally advanced esophagogastric cancer induces anemia and therefore leads to preoperative blood supplementation in a considerable number of patients. Data indicate that this may counteract the beneficial effects of neoadjuvant treatment.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Erythrocyte Transfusion; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Retrospective Studies

We report the effects and toxicities of intravenous administration of cisplatin, 5-FU and high-dose leucovorin for advanced esophageal cancer. Eight patients were registered and sixteen lesions were measurable. Of these sixteen lesions, thirteen were primary or synchronous metastatic lesions, and the response was 69%. Three were recurrence lesions, and the response rate for them was 0%. Including seven neoadjuvant cases, ten patients had oral mucositis, and seven patients had appetite loss. Other toxicities were diarrhea, myelosuppression, renal dysfunction, and alopecia. All were reversible after administration. It is suggested that this treatment regimen is a superior neoadjuvant chemotherapy with low toxicity.

Topics: Aged; Aged, 80 and over; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local

A 51-year-old male was assessed as having esophageal squamous cell carcinoma with trachea invasion and cervical lymph node metastasis. After one course of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU) and Leucovorin (LV), the patient had progressive disease (PD) of the primary lesion and metastatic lymph nodes, and a side effect of severe nausea. One course of nedaplatin, 5-FU and LV combined with radiation was performed alternatively. The effect was evaluated as a partial response (PR) of the primary lesion and metastatic lymph nodes. There were no adverse side effects such as nausea or renal dysfunction except for pancytopenia of grade 2. Increased serum levels of vascular endothelial growth factor (s-VEGF) decreased after the chemoradiotherapy and increased again during continued radiotherapy alone. More information is needed as to whether changes in s-VEGF relate to the clinical effects of the treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Endothelial Growth Factors; Esophageal Neoplasms; Fluorouracil; Humans; Intercellular Signaling Peptides and Proteins; Leucovorin; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Organoplatinum Compounds; Tracheal Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The effect of preoperative chemotherapy on prognosis is still controversial. We have investigated the relationship between responses to preoperative chemotherapy and prognosis after curative operations in patients with esophageal squamous cell carcinoma. Thirty-nine patients received preoperative chemotherapy with continuous infusion of 500 mg/m2 of 5-fluorouracil (5-FU) and intravenous injection of 20 mg/m2 of leucovorin every 12 hours for 5 days. On the 5th day alone, 70 mg/m2 of cisplatin was also infused. The effect was evaluated approximately 14 days after the end of one course of chemotherapy. The rates of responders and non-responders were 64.1% and 35.9%, respectively. After an interval of 21-28 days, transthoracic esophagectomy was performed. Significant histological effect by chemotherapy was found in responders compared to non-responders (P < 0.05). Responders had a significantly better prognosis than non-responders by Log-rank test (P < 0.01). This suggests that preoperative chemotherapy may contribute to better prognosis when the tumor is sensitive to chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Case-Control Studies; Cisplatin; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Preoperative Care; Prognosis; Survival Rate; Time Factors

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Choroid Neoplasms; Combined Modality Therapy; Esophageal Neoplasms; Fatal Outcome; Fluorescein Angiography; Fluorouracil; Humans; Leucovorin; Male; Middle Aged

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoma, Squamous Cell; Case-Control Studies; Chemotherapy, Adjuvant; Cisplatin; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Probability; Prognosis; Statistics, Nonparametric; Survival Analysis; Treatment Outcome

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

The best chemotherapeutic regimen for advanced carcinoma of the esophagus remains to be determined. We have evaluated a combination of carboplatin, cisplatin and 5FU modulated by folinic acid. Patients. Twenty-seven patients (median age 57 yrs) with an unresectable carcinoma of the esophagus were included in this trial: 9 patients with a local relapse after surgery, 6 patients with a locally advanced (T4) tumor, and 12 patients with metastasis. Treatment schedule. Initial chemotherapy : carboplatine IV d1, AUC4; 5FU: bolus injection of 400 mg/m2 d1, followed by a continuous infusion of 600 mg/m2/24 h, d1 and d2; folinic acid (200 mg/m2) IV, before the 5FU bolus, d1 and d2; cisplatine 80 mg/m2, d3; on d15 and d16, 5FU and folinic acid were repeated with the same schedule. The second cycle began on d28. Concomitant chemo-radiotherapy with 5FU (1,000 mg/m2 d1 to d3), cisplatine (50 mg/m2 d1 and d2) and external irradiation (20 Gy in 10 fractions from d1 to d12) was then performed, for three cycles (until a total dose of 60 Gy). Results.. neutropenia grade 3-4 (32%), thrombopenia grade 3-4 (18%). More important, a lymphopenia (< 500/mm3) was noted in 12 patients (43%). Accordingly, 4 serious infectious complications were observed, with three toxic deaths. Objective response rate: 44% after initial chemotherapy; 75% after chemoradiotherapy, with 8 complete responses (38%). Median survival was 7.4 months, with a one- and two-year survival of 33% and 17,8%, respectively. Conclusion. This association of cisplatin, carboplatin, and 5FU did not offer a better response rate than the classical 5FU-cisplatinum association. But serious infectious complications occurred during the trial. We do not recommended further evaluation of this biplatinum therapy with 5FU in advanced esophageal carcinomas.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Humans; Kidney; Leucovorin; Lymphopenia; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Analysis; Thrombocytopenia

Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy.. Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically.. The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04).. PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Monitoring; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorodeoxyglucose F18; Humans; Leucovorin; Male; Middle Aged; Patient Selection; Preoperative Care; Prognosis; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Statistics, Nonparametric; Survival Rate; Tomography, Emission-Computed

The purpose of this study was to evaluate the efficacy and toxicity of an induction chemotherapy schedule followed by high-dose radiotherapy and concurrent chemotherapy for locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Patients were treated with three courses of fluorouracil, leucovorin, etoposide, and cisplatin-containing induction chemotherapy followed by high-dose external beam radiotherapy to 65 Gy in 6 weeks for T4 and obstructing T3 tumors. Transversable T3 tumors received 60 Gy in 6 weeks by external radiotherapy, followed by two high-dose-rate esophageal brachytherapy fractions of 4 Gy in 5-mm tissue depth. Concurrent to radiotherapy, cisplatin and etoposide were given. Long-term survival of 22 patients was 41% and 31% at 2 and 3 years, respectively, with a median follow-up of 39 months. The probability of locoregional tumor recurrence was 60% at 3 years for all patients and 30% for those with a partial or complete response to induction chemotherapy. Acute toxicity of this schedule was moderate. Long-term survivors had a good swallowing function. This schedule offers a considerable chance of long-term survival for patients with locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Local in-field recurrences are the main risk after definitive radiochemotherapy. Dose escalation of radiotherapy is possible because of the observed low late toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Squamous Cell; Cisplatin; Cohort Studies; Combined Modality Therapy; Deglutition Disorders; Drug Administration Schedule; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prognosis; Quality of Life; Survival Analysis

Many combination patterns of chemotherapy and radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer indicate that the optimal doses of chemotherapeutic agents and of chemotherapy and radiotherapy regimens remain unclear. The feasibility and promising outcome of our newly developed definitive CRT for nonsurgical management of esophageal cancer, essentially based on the theoretical backgrounds of the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, is investigated.. Six nonoperated esophageal cancer patients were treated by daily concurrent CRT, which consisted of continuous 5-fluorouracil administration with leucovorin, combined with a low dose of daily cisplatin administration before each fraction of radiation. Response to CRT and toxicities and survivals were evaluated.. Complete and partial responses were seen in 2 patients each. Histologic examination of the biopsy specimens in the primary site showed no cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other 2 patients showed good-quality survival, having dramatic relief from dysphagia. There were no treatment-related deaths.. The daily concurrent CRT is rational and promising and compares well with other series of definitive CRT. The CRT based on the theoretical background is feasible as a nonsurgical management option for esophageal cancer patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose Fractionation, Radiation; Drug Administration Schedule; Esophageal Neoplasms; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Radiotherapy Dosage; Survival Analysis

We conducted a prospective study on neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. Thirty-two patients, 30 men, 2 women, mean age 56.2-8.9 years, with resectable squamous celi carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were included. Chemotherapy, CDDP (80 mg/m2: D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and 1-folinic acid (200 mg/m2, DI-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg Injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelests, mucosite's) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n = 18), persistent microscopic residues (n = 4), or not significant modification (n = 4). Survival at 1, 3, and 5 years was 82, 47, and 47% and disease-free survival was 77, 47, and 47% respectively. This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 5-year survival reached 47%, a very high rate in our experience.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome

In the present study, the expression of cyclin D1, as detected by immunohistochemistry, was compared with other prognostic variables and its prognostic impact was evaluated in a group of 172 patients with squamous cell carcinoma (SCC) of the esophagus who underwent potentially curative resection therapy and in a second group of 38 patients with SCC of the esophagus who were treated by combined modality therapy (radiochemotherapy +/- surgery). Expression of cyclin D1 in surgically treated carcinomas correlated negatively with tumor differentiation (p = 0.026) but positively with mitotic activity (p = 0.0199) and nodal status (p = 0.040). There were no significant correlations with pT category. Patients with cyclin D1-positive carcinomas showed significantly worse overall survival than patients with cyclin D1-negative carcinomas, both in univariate (p = 0.0016) and in multivariate survival analyses (p = 0.0038). Expression of cyclin D1 in carcinomas with multimodal treatment was correlated with poor response to chemotherapy (p = 0.026) but not with overall survival. We thus consider expression of cyclin D1 to be an important parameter, predicting an unfavorable overall survival of surgically treated esophageal cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cyclin D1; Epirubicin; Esophageal Neoplasms; Esophagus; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucous Membrane; Prognosis; Survival Rate

A 63-year-old male with an esophageal cancer invading the bronchus was treated with radiation therapy (70 Gy) from November 1995, resulting in the disappearance of the lesion. He was later readmitted due to dysphagia from the recurrence of the esophageal cancer. We diagnosed, by endoscopic and chest CT scan findings, that the esophageal cancer was invading the right bronchus. We inserted an expandable metallic stent endoscopically, and the patient could eat well. We performed two courses of FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide and cisplatin) from November 12, 1997. He then suffered from an esophagobronchial fistula, but was cured by a covered expandable metallic stent replacement. No esophageal stenoses or recurrences were seen endoscopically and he could eat well on December 7, 1998. The standard modality of treatment for patients with advanced esophageal cancer invading adjacent structures is not yet established, and the prognosis for such patients remains quite poor. We performed combination therapy with an expandable metallic stent replacement and FLEP chemotherapy, and improved the patient's quality of life. This form of therapy was thus proved useful for patients with esophageal cancer invading adjacent structures.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bronchial Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Etoposide; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Stents

The effects of ondansetron hydrochloride (OND) were studied through 11 courses of chemotherapy, including 70 mg/m2 of cisplatin, in 9 patients with advanced esophageal cancer. During the observation period of 5 days, 4 mg of OND was given intravenously on the day of cisplatin infusion and orally for consecutive 4 days, and nausea was controlled by over 70%. Vomiting was controlled by over 80%. The inhibitory effect of OND on nausea and vomiting was found in 72.7% on the day of cisplatin injection and 88.9% overall. No other side effects of OND except slight increases in total bilirubin and LDH were found in any patient. These findings suggest that intravenous and oral administration of OND may inhibit chemotherapy-induced nausea and vomiting in patients with advanced esophageal cancer.

Topics: Administration, Oral; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Nausea; Ondansetron; Vomiting, Anticipatory

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

Postoperative complications were investigated in 72 patients who received neoadjuvant therapy with esophagectomy. Preoperative chemotherapy consisted of 5-fluorouracil (700 mg/m2/day, on days 1 to 5), cisplatinum (70 mg/m2/day, on day 1) and leucovorin (20 mg/m2/day, on days 1 to 5). Preoperative chemoradiotherapy consisted of cisplatinum combined chemotherapy and radiotherapy (total dosage of 30-70 Gy). The incidence of postoperative pneumonia (16%) and anastomotic leakage (24%) in the preoperative chemotherapy group was slightly higher than that in the control group (n = 506), and mortality (6.0%) after esophagectomy in the preoperative chemotherapy group was higher than that (2.4%) of the control group. Postoperative morbidity and mortality were observed more frequently in patients who received two cycles of the chemotherapy than those receiving only one cycle. Postoperative complications occurred more frequently in patients suffering high grade toxicities due to the preoperative chemotherapy. The highest preoperative serum creatinine value correlated to that of postoperative period (r = 0.6494). The use of the preoperative chemoradiotherapy with a total exposure dosage of 60 Gy or more significantly increased the postoperative pneumonia rate (67%; p < 0.05) compared to the group receiving 40 Gy or less. The mortality rate (33%) also increased. The second cycle of the preoperative chemotherapy should be cancelled if patients suffer high grade toxicities during or after the first cycle, and the total exposure dosage of the preoperative chemoradiotherapy should be limited to 40 Gy or less.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Pneumonia; Postoperative Complications; Radiotherapy Dosage; Surgical Wound Infection; Survival Rate

A 67-year-old man was diagnosed as having a type 3 advanced esophageal carcinoma by barium swallow and endoscopy. Biopsy specimens showed well-differentiated squamous cell carcinoma with positive immunostaining for p53, C-erb B-2 and negative for bcl-2. Two courses of chemotherapy using 5-FU, leucovorin and CDDP were performed before operation. Because no cancer cells were present in the surgical specimens, the effect was evaluated as grade 3. This neoadjuvant chemotherapy may be effective for esophageal carcinoma with a possible apoptosis mechanism.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Staging; Preoperative Care

The purpose of this trial was to examine the feasibility of intensive, sequential chemo- and radiochemotherapy followed by surgery in patients with locally advanced carcinomas of the lower oesophagus and the gastro-oesophageal junction (GO junction). The chemotherapy consisted of two courses of 6 weekly administrations of 5-fluorouracil (5-FU) (2.0 g/m2, 24 h infusion) and folinic acid (FA) (500 mg/m2, 2 h infusion) combined with twice weekly cisplatin (50 mg/m2, 1 h infusion). Irradiation of 30 Gy was given concurrently with one course of cisplatin and etoposide. 25 patients with locally advanced (T3-T4 NX M0) squamous cell or adenocarcinoma of the lower oesophagus and GO junction were included and evaluated. Toxicity was usually mild to moderate (WHO grade 1 and 2) with mucositis as the most important side-effect of the pre-operative treatment. Of the patients, 94 and 88% completed the chemo- and radiochemotherapy according to the protocol, respectively. A major response (= partial remission with subjective improvement) to chemotherapy was achieved in 6/10 patients with squamous cell carcinoma and 10/15 with adenocarcinoma. 19 patients had subsequent surgery and complete resection was achieved in 16 (3 patients had intra-abdominal metastases observed at laparotomy). The operative mortality rate was 16% (3/19). 10 of the 16 patients with tumour resection had a pathological complete response. 15 patients (43%) remain alive at a median follow-up of 20 months and the median survival exceeds 16+ months. Our data suggest that this intensive pre-operative chemoradiotherapy programme is feasible and remarkably effective in patients with locally advanced carcinomas of the lower oesophagus or GO junction.

Topics: Adenocarcinoma; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagogastric Junction; Etoposide; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Survival Analysis; Treatment Outcome

We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction.. Thirty-two patients, 30 men, 2 women, mean age 56.2+/-8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I=4, IIA=4, IIB=13, III=11) were included. Chemotherapy, CDDP (80 mg/m2 D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and l-folinic acid (200 mg/m2, D1-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy.. No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets, mucositis) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n=18), persistent microscopic residues (n=4), or not significant modification (n=4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively.. This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.

Topics: Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Radiotherapy Dosage; Treatment Outcome

Available data concerning the treatment of patients with advanced T4 esophageal carcinoma are limited. A consecutive series of 42 patients with advanced T4M0 epidermoid carcinoma of the esophagus were studied from June 1987 to July 1992. The aim of this study was to evaluate the efficacy of various therapeutic modalities, and further evaluate the therapeutic options. The various therapeutic modalities included the following: Group I, feeding jejunostomy or endoesophageal intubation, 6 patients; Group II, palliative subtotal esophagectomy only, 8 patients; Group III, bypass procedures without tumor resection, 9 patients; Group IV, nutritional support and then treatment with irradiation (n=8) or concurrent radio-chemotherapy (n=4), 12 patients; Group V, subtotal esophagectomy, followed by aggressive concurrent radiochemotherapy, 7 patients. The total prescribed irradiation dose was 60 Gy (10 Gy/5 fractions/week). A combination regimen of chemotherapy consisted of cisplatin, 5-fluorouracil, and leucovorin (PFL regimen). For the patients undergoing esophagectomy or bypass procedures (n=24), the rates of operative complication and mortality were 45.8% and 25%, respectively. Side effects of adjuvant therapy (n=24) consisted of main airway irritation (100%), mucositis or gastrointestinal symptoms (83.3%), hematologic toxicity (79.2%), esophagitis or gastric ulcer (62.5%), alopecia (37.5%), and pneumonia (20.8%). The mortality due to toxicity of adjuvant therapy was 21.1% (4/19 patients). The mean survival times for each of the different groups was 1.9+/-0.5 months for Group I, 4.8+/-1.6 months for Group II, 5.2+/-1.2 months for Group III, 7.3+/-2.0 months for Group IV, and 20.3+/-2.5 months for Group V, respectively. Compared with patients of Groups I--IV, the Group V patients had a significantly superior one-year survival rate (P<0.01). Our results demonstrated that esophagectomy followed by concurrent irradiation and PFL combination chemotherapy may provide a significant improvement in the quality of life and survival for appropriate patients with advanced T4M0 epidermoid carcinoma of the esophagus. Furthermore, more than one cycle of PFL regimen chemotherapy may result in a better prognosis. During the performance of such an aggressive treatment, the utmost care must be taken with the patient's nutrition and to prevent pulmonary complications.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Radiotherapy, Adjuvant; Survival Rate

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytomegalovirus Infections; Enteritis; Esophageal Neoplasms; Fluorouracil; Humans; Ileitis; Interferon-alpha; Leucovorin; Male; Middle Aged

We designed a trial of intensive multimodality therapy for carcinoma of the esophagus and gastroesophageal junction to assess tumor response and operability after neoadjuvant chemotherapy and to determine the impact of trimodality therapy on longterm survival.. Thirty-two patients with resectable (clinical stage IIa, n = 17; IIb, n = 1; III, n = 14) squamous cell cancer (n = 15) or adenocarcinoma (n = 17) were treated with neoadjuvant chemotherapy (cisplatin, 5-fluorouracil, leukovorin), resection, and postoperative chemoradiotherapy (hydroxyurea, 5-fluorouracil; 50-66 Gy).. Use of neoadjuvant chemotherapy yielded the following results: a measurable clinical response in 22 patients, stable disease in eight patients, disease progression in one patient, and death in one patient. Thirty-one patients underwent resection, with the following results: two operative deaths (6.5%) and nonfatal morbidity in 17 (59%); the median hospital stay was 13 days. Pathologic staging was stage 0, n = 1; I, n = 2; IIa, n = 11; IIb, n = 5; III, n = 7; and IV, n = 5. Postoperative chemoradiotherapy was completed in 23 patients with one death, for an overall treatment-related mortality rate of 12.5% (four of 32). At a mean follow-up of 22.5 months, median survival is 19.7 months and 14 patients are alive and disease free.. Neoadjuvant therapy for cancer of the esophagus and cardia results in good tumor response. Esophagectomy in this setting can be accomplished with acceptable morbidity and mortality. Results of an interim analysis of survival are encouraging and suggest that further investigation of this regimen is warranted.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Hydroxyurea; Leucovorin; Male; Middle Aged; Neoplasm Staging; Postoperative Care; Radiotherapy, Adjuvant; Remission Induction; Survival Rate

Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy added radiation therapy was performed for the treatment of 62-year-old male patient with advanced esophageal cancer who had liver cirrlosis. After the treatment, esophageal lesion disappeared. Only minimal side effect occurred during the treatment. Biochemical modulation chemotherapy combined with radiation therapy is useful for advanced esophageal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Radiotherapy, Adjuvant; Radiotherapy, High-Energy; Remission Induction

From March 1992 to May 1994, 105 patients with esophageal carcinoma patients were treated with CF/5-Fu-DDP (group A, n = 40) or 5-Fu-DDP (group B, n = 65) protocol. The response rate (CR+PR) was 80% in group A and 60% in group B. (P < 0.01) Induction chemotherapy was followed by surgery or radiation therapy. The incidence of nausea, vomiting, cardiotoxicity and leukopenina was higher in group A than in group B. Buccal mucositis, diarrhea, abdomenal pain and skin pigmentation were noted only in group A. However, the toxic effects were tolerable. The results suggest that the CF/5-Fu-DDP regimen is more effective than 5-Fu-DDP regimen and may be one of the best chemotherapy regimens for the treatment of esophageal carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Vomiting

In a 4-year period (1988-1991) 122 patients with a squamous cell carcinoma of the esophagus were studied prospectively and analysed. 64 patients of them could be primary resected (primary resectability rate 52%), 36 patients were in general inoperable and 22 patients had an advanced stage of cancer with local inoperability. Due to a preoperative combined radiotherapy and chemotherapy 16 of the 22 patients with local inoperability had a clinical remission of the tumor (73%). 11 patients (50%) showed a histological verified down staging and 3 cases of them a complete remission (no primary tumor was found, no infiltration of the regional lymphnodes and no metastatic disease). Curative resection was possible in 14 of 16 patients with clinical remission (2 patients refused surgical treatment). So the resectability rate now increases from 52 to 63%. We conclude that there was no increased rate of postoperative complications or mortality in the combined radio-/chemotherapy group compared with the primary resected patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagus; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Neoplasm Staging; Preoperative Care; Radiotherapy Dosage; Survival Rate

Current multimodality treatment of thoracic esophageal carcinoma in our institution was described. The rate of superficial carcinomas is increasing in recent years, and they are treated by endoscopic mucosal resection (EMR), transhiatal esophagectomy (THE) or with the thoracotomy approach. Treatment is based on precise diagnosis of the depth of cancer invasion and nodal involvement using endoscopy with endoscopic ultrasound (EUS). Three-field lymphadenectomy for thoracic esophageal carcinoma, including superficial one, was started in 1983 as a standard operation, and its indications have been gradually decreasing for the past 10 years. As a result of accurate, individualized treatment, life table analysis revealed no significant difference between 2- and 3-field lymphadenectomy. Multimodality treatment of advanced cases is mainly composed of 3-field lymphadenectomy. Adjuvant chemotherapy of systemic therapy is regarded as more important than concurrent irradiation of local therapy. Recently powerful chemotherapy is becoming more frequent pre- or postoperatively. Our routine regimen is CDDP and infusional 5-FU with leucovorin as a biochemical modulator.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Esophageal Neoplasms; Esophagus; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Radiotherapy Dosage; Survival Rate

Recently, esophageal carcinoma has shown a wide variation in spread, from carcinoma in situ to the far-advanced type. Therefore, the treatment must be performed on the basis of accurate clinical stagings, and not only the prognosis but also the quality of life of patients should be considered. Surgical resection has been regarded as standard treatment for patients with advanced carcinoma, but in some cases, preoperative treatments should be added to perform curative resections. Our objectives in preoperative (neoadjuvant) chemotherapy with cisplatin and other chemotherapeutic agents are three-fold: 1) To reduce the extent of direct invasion of neighboring structures (e.g., aorta, trachea or bronchus). 2) To reduce the degree of lymph node metastasis. 3) To preserve the larynx in cases of cervical esophageal carcinoma. For the past 4 years, we treated 13 cases of advanced esophageal carcinoma with this chemotherapy method preoperatively. Two of 13 patients showed a partial clinical response, including one with no viable carcinoma cells pathologically, and 4 had a minor clinical response. However, the impact on overall survival must be further investigated. We conclude that this multimodality treatment is effective for local tumor control, but should be applied for selected patients with careful management of its side effects.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Preoperative Care; Survival Rate

Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Postoperative Complications; Prospective Studies; Radiotherapy Dosage; Survival Rate

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

We treated 20 patients with squamous cell carcinoma of the esophagus with the following regimen: cisplatin = 100 mg/m2 i.v. day 1, HDFA = 200 mg/m2 i.v. day 1 to 5, 5-fluorouracil = 370 mg/m2 i.v. day 1 to 5 repeated every 28 days. Among the 17 evaluable patients, 4 (23%) had a partial remission, 6 had stable disease while 7 progressed. The median survival for all patients was 6+ months. Grade III or IV toxicity included 2 patients with grade III leukopenia, 1 with grade III thrombocytopenia, 1 patient with grade IV and 3 patients with grade III oral mucositis, 3 patients with grade III diarrhea. The regimen did not seem particularly active in the treatment of squamous cell carcinoma of the esophagus and had manageable but substantial toxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Remission Induction

From January to November, 1981, 28 patients with unresectable squamous cell carcinoma of the esophagus were treated with two cycles of chemotherapy combining vincristine (V), methotrexate (M), folinic acid rescue, and cisplatin (P) on days 1 and 21. Split-course radiation therapy was delivered thereafter from day 42 on. Hematologic, renal, and neurologic tolerance was acceptable, but most of the patients experienced nausea and vomiting. Results evolution at day 40 showed a 61% partial response (PR) rate and a 7% complete response (CR) rate. One month after the end of radiation therapy, 43% PR and 32% CR were obtained. Median response duration was 8 months. Median survival was 11.6 months for patients overall, yielding 12.9 months for responders and 5.9 months for nonresponders. Based on the response rate obtained with combined chemotherapy, a randomized trial of VMP initial chemotherapy is currently being undertaken by our cooperative group to study whether such an initial treatment could improve resectability and radiation-mediated local control along with survival rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Time Factors; Vincristine; Vomiting