s-1-(combination) and Colonic-Neoplasms

S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride.. A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. At the end of the S-1 administration period in every course, his serum triglyceride level was found to be elevated. Finally, it reached grade 4, without any symptoms of acute pancreatitis in the fifth course, and fenofibrate 80 mg once a day was administered.. S-1 administration induced hypertriglyceridemia owing to the elevated serum triglyceride; however, a contrasting result was observed in the S-1 withdrawal period and during the S-1-cessation cycle. Since dietary intake was poorer during the S-1 administration period, it is considered that S-1 might have disturbed lipid metabolism. Further, we know that capecitabine, which is a prodrug of fluorouracil, also induces hypertriglyceridemia. As the end product of these medicines is fluorouracil, the presence of fluorouracil or its metabolizing enzymes, the genetic background of the patient might have affected the results. We have to be aware of the risk of asymptomatic and temporal occurrence of hypertriglyceridemia by S-1 administration for the early detection with appropriate pre-emptive treatment.

Topics: Acute Disease; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Combinations; Humans; Hypertriglyceridemia; Male; Middle Aged; Oxonic Acid; Tegafur

Our patient was a 58-year-old man who was diagnosed with a large bowel obstruction caused by ascending colon cancer, together with multiple liver metastases for which a right hemicolectomy was performed. After the operation, he developed disseminated intravascular coagulation(DIC)and severe anemia. Bone marrow biopsy findings led to a diagnosis of disseminated carcinomatosis of the bone marrow caused by colon cancer. We administered S-1+oxaliplatin(SOX) and bevacizumab( BV)chemotherapy, which improved the DIC. The patient was discharged from the hospital. After a total of six courses of chemotherapy, the carcinoma became resistant. We changed the drug regimen and his clinical condition improved. He survived for 292 days from the onset of disease.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Marrow Neoplasms; Chemotherapy, Adjuvant; Colonic Neoplasms; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

In June 2010, a 62-year-old man underwent right hemicolectomy with transverse colostomy for advanced ascending colon cancer with peritoneal dissemination(pSE, pN3H0P3M0, fStage IV, R2). One month after surgery, systemic chemotherapy (combination regimen of oxaliplatin injection and S-1 per os; SOX regimen) was introduced for the residual lesion. After completing 4 courses of the SOX regimen, peritoneal dissemination was not detected by abdominal computed tomography. In the same month, laparotomy was performed to close the temporary stoma, in which the lack of peritoneal dissemination was confirmed. After the stoma was closed, although no chemotherapy was administered because of patient preference, he has been free from relapse of the peritoneal dissemination, according to his latest follow-up examinations in June 2012. In this case, resection of the primary lesion immediately followed by a short period of systemic chemotherapy resulted in good control of peritoneal dissemination. Because the effect of these therapies allowed him to undergo stoma closure and to refuse further chemotherapy, he has been able to maintain his quality of life. In cases of reduction surgery for advanced colorectal cancer with unresectable peritoneal dissemination, a minimal resection including the primary lesion to avoid perioperative complications, which could permit the immediate start of systemic chemotherapy, could result in good control of peritoneal dissemination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colostomy; Combined Modality Therapy; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Quality of Life; Tegafur

Prognosis of patients with advanced mucinous cystadenocarcinoma of the appendix (AMCA) is extremely poor. However, there has been no established treatment strategy. We preliminary report here a successfully treated case with AMCA using intensive cytoreductive surgery and chemotherapy. A 61-year-old woman had a right lower abdominal pain and was diagnosed as acute appendicitis. At surgery, about 5 cm tumor with mucosal fluid was detected at the distal part of the appendix. The tumor was invading the ileum and bladder. We performed appendectomy with tumor, partial resection of the small intestine and debridement of mucosal fluid. Histopathology revealed AMCA invading the ileum and bladder. After non curative surgery, we started S-1 plus cisplatin chemotherapy, which S-1 was given orally, twice daily for 3 consecutive weeks, and cisplatin was given intravenously on day 1, 8 and 15 followed by a 3-week rest period. After 6 courses starting with chemotherapy, a complete response was obtained. We followed by S-1 until two years after the initial surgery. At 36 months after the initial surgery, CT scan demonstrated a peritoneal recurrence. Then, she underwent intensive peritonectomy with intraperitoneal hyperthermic chemotherapy. Currently, she had no apparent recurrence for 59 months after initial surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendix; Cisplatin; Colonic Neoplasms; Cystadenocarcinoma, Mucinous; Drug Combinations; Female; Humans; Hyperthermia, Induced; Middle Aged; Oxonic Acid; Remission Induction; Tegafur; Time Factors; Tomography, X-Ray Computed

Chemotherapy that targets metastatic colorectal cancer originally developed in Europe and the US, and was introduced to Japan in April, 2005, where it has since headed toward full scale clinical applications. This event created an opportunity to re-evaluate the role of postoperative adjuvant chemotherapy in Japan. In Europe and the US, adjuvant therapy has centered on the intravenous administration of leucovorin/fluorouracil, while in Japan, it has been long-term continuous administration of oral fluoropyrimidine preparations. Despite this difference in historical background,guidelines created in 2005 recommend both LV/5-FU and LV/UFT regimens and there has been increased application of evidence-based adjuvant chemotherapy. The benefits of postoperative adjuvant chemotherapy in stage II and III (high risk of recurrence) colorectal cancer patients have also come to be recognized. Examination of a new survey of 100 medical specialists on the current state of adjuvant chemotherapy for colorectal cancer in Japanese clinical settings revealed that for stage III patients, there is a tendency to choose treatment based on evidence gathered from both home and abroad. In contrast, a solid majority (60%) of stage II patients are treated exclusively with oral fluoropyrimidine despite a lack of, or limited evidence of efficacy. At the same time, half of the physicians who treated stage II patients with adjuvant chemotherapy initially attempted to identify those with a high risk of cancer recurrence and treat them accordingly; which was a breakthrough in the clinical treatment approach. While ongoing comparative Japanese clinical studies that use adjuvant chemotherapy for the treatment of colorectal cancer were noted, consideration was also given to the desired future direction clinical research should take.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Europe; Evidence-Based Medicine; Fluorouracil; Humans; Irinotecan; Japan; Leucovorin; Neoplasm Staging; Oxonic Acid; Practice Guidelines as Topic; Rectal Neoplasms; Tegafur; United States; Uracil

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Enzyme Inhibitors; Fluorouracil; Humans; Oxaloacetates; Oxonic Acid; Tegafur; Uracil

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colonic Neoplasms; Docetaxel; Drug Administration Schedule; Drug Combinations; Drug Delivery Systems; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

Recently, the demand for more useful therapies for cancer patients has increased. We describe in this paper a therapeutic modality based on a self-rescuing concept (SRC), and which features dual activity, i.e., an effect-enhancing activity and an adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: the oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil, which is used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1 is a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo, respectively. A clinical pharmacology study was conducted to examine blood concentrations of 5-FU after twice-a-day administration of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were found to be 60 to 200 ng/ml in all twelve patients examined. The overall response rate was 44.6% (45/101). In addition, the incidence of adverse reactions judged to be grade 3 or higher was 10% or less. We have also reported a combination therapy with 5-FU (civ) (5-FU: 250 to 350 mg/body, 24-hour cvi, consecutive days) and low-dose cisplatin (CDDP: 3 to 5 mg/body, i.v., 5 days/week), in which CDDP was used as a modulator of 5-FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163 patients with various gastrointestinal cancers other than pancreas cancer. The incidence of the adverse reactions of nausea and vomiting which were judged to be grade 3 or higher was 2.5% (4/163). The incidences of other adverse reactions were 1% or less. In line with the theory and practice of combination therapy with 5-FU (cvi) 24 hr cvi; 5-FU: 750 to 1,000 mg/body/day on Monday, Wednesday, and Friday (withdrawal on Tuesday, Thursday, Saturday and Sunday) intermittent administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive administration was utilized in which there was a difference in cell cycle between gastrointestinal mucosal cell and tumor cell, or between bone marrow cell and tumor cell. Few adverse reactions, e.g., diarrhea and stomatitis, were observed despite the overall response rate being as high as 52.4% (22/42). The incidence of adverse reaction judged to be grade 3 or higher was as low as 9.3% (5/54), with an incidence of 9.3% (5/54) in Grade 3 or higher myelotox

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Fluorouracil; Humans; Infusions, Intravenous; Oxonic Acid; Pancreatic Neoplasms; Pyridines; Rectal Neoplasms; Tegafur

Adjuvant chemotherapy is an accepted treatment to improve survival rates in patients with stage III colon cancer, and regimens including oxaliplatin have been shown to be superior to those containing 5-FU alone. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) as adjuvant chemotherapy for patients with stage III colon cancer following curative resection.. Patients with colon cancer who underwent curative resection were enrolled and received oral S-1 40-60 mg twice daily on days 1-14 every 3 weeks plus intravenous oxaliplatin 130 mg/m. Between February 2014 and December 2014, 89 patients were enrolled. One patient was excluded from the analysis because of ineligibility, and the remaining 88 patients were included. The rate of protocol treatment completion was 72.3%. The relative dose intensity of S-1 and oxaliplatin was 72% and 76.3%, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). The incidence of grade 2 neuropathy has decreased from 8.1 to 2.7% after 3 years of the therapy. Three-year disease-free survival rate was 73.9% (95% CI 63.8-81.9), and 3-year overall survival rate was 94.3% (95% CI 86.8-97.6) CONCLUSIONS: C-SOX is a safe and feasible adjuvant chemotherapy regimen in patients with stage III colon cancer undergoing curative resection.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Survival Rate; Tegafur

Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer.. The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events.. In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm.. One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur; Uracil

Postoperative adjuvant chemotherapy for patients with stage III Colorectal cancer (CRC) is now internationally accepted as standard care for improving patient outcomes. The Adjuvant Chemotherapy Trial of S-1 for Colorectal Cancer (ACTS-CC) confirmed the non-inferiority of S-1 to tegafur/urcail/leucovorin in terms of overall survival and disease-free survival in patients with stage III CRC after curative surgery. However, the 6-month completion rate of S-1 treatment was 76.5% in the ACTS-CC. Therefore, treatment completion remains an unresolved problem.. A randomized phase II trial was designed to evaluate the efficacy and safety of oral daily administration and alternate-day administration of S-1 as adjuvant chemotherapy in curatively resected stage III CRC. Enrolled patients were assigned to either S-1 daily administration (Arm A) or alternate-day S-1 administration (Arm B). Assigned treatment will start within 8 weeks after surgery. In both arms, S-1 dosing (oral) will be based on body surface area (80 mg/day for body surface area<1.25 m2, 100 mg/day for 1.25-1.5 m2, or 60 mg/day for >1.5 m2). In Arm A, S-1 will be administered orally for 28 days, followed by a 14-day rest. Administration will be conducted for 24 weeks from the date of therapy start. In Arm B, S-1 will be administered orally on alternate days for 28 weeks from the date of the start of therapy. After treatment, all patients will be observed without additional therapy unless recurrent lesions or other cancer lesions occur. The primary endpoint is treatment completion rate. Secondary endpoints include 3-year disease-free survival, compliance, and adverse events.. Previously, S-1 alternate-day intake maintained the efficacy of chemotherapy while reducing adverse effects for patients with R0-resected stage II/III gastric cancer. Improvement of chemotherapy completion rate for patients with colorectal cancer will lead to an improved patient prognosis. Therefore, a randomized phase II trial has been designed to examine the efficacy of alternate-day versus current standard daily S-1 administration as adjuvant chemotherapy for R0-resected stage III colorectal cancer.. This study was registered on 18 February 2014 with University Hospital Medical Information Network Clinical Trials Registry: UMIN000013185.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Dosage Calculations; Humans; Medication Adherence; Middle Aged; Oxonic Acid; Rectal Neoplasms; Research Design; Tegafur; Young Adult

S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV).. Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years.. A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups.. Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer.. NCT00660894.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur; Uracil; Young Adult

Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer.. Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m(2)) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle.. The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at <10%, other than diarrhea (10.9%).. In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur

Although, in Western countries, oxaliplatin-based regimens have been established as a gold standard treatment for patients with stage III or high risk stage II colon cancer after curative resection, in Japan fluorouracil-based regimens have been widely accepted and recommended in the guidelines for adjuvant settings in patients with stage III colon cancer. S-1, an oral preparation evolved from uracil and tegafur, has equivalent efficacy to uracil and tegafur/leucovorin for treating patients with advanced colorectal cancer and might be a suitable regimen in an adjuvant setting. However, the completion rate of the standard six-week cycle of the S-1 regimen is poor and the establishment of an optimal treatment schedule is critical. Therefore, we will conduct a multicenter randomized phase II trial to compare six-week and three-week cycles to establish the optimal schedule of S-1 adjuvant therapy for patients with stage III colon cancer after curative resection.. The study is an open-label, multicenter randomized phase II trial. The primary endpoint of this study is three-year disease-free survival rate. Secondary endpoints are the completion rate of the treatment, relative dose intensity, overall survival, disease-free survival, and incidence of adverse events. The sample size was 200, determined with a significance level of 0.20, power of 0.80, and non-inferiority margin of a 10% absolute difference in the primary endpoint.. Although S-1 has not been approved yet as a standard treatment of colon cancer in an adjuvant setting, it is a promising option. Moreover, in Japan S-1 is a standard treatment for patients with stage II/III gastric cancer after curative resection and a promising option for patients with colorectal liver metastases in an adjuvant setting. However, a six-week cycle of treatment is not considered to be the best schedule, and some clinicians use a modified schedule, such as a three-week cycle to keep a sufficient dose intensity with few adverse events. Therefore, it will be useful to determine whether a three-week cycle has an equal or greater efficacy and tolerance to side-effects compared with the standard six-week cycle schedule, and thus may be the most suitable treatment schedule for S-1 treatment.. The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000006750.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Clinical Protocols; Colectomy; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Humans; Japan; Neoplasm Staging; Oxonic Acid; Research Design; Tegafur; Time Factors; Treatment Outcome

The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis.. Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated.. Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively.. Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Tegafur; Uracil

The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer.. S-1 was administered orally at 80 mg/m(2) per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m(2) per day, stepping up to 100, 120 or 150 mg/m(2) per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed.. A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m(2), because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m(2). Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0-14.0 months).. A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Injections, Intravenous; Irinotecan; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Tegafur

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

Trifluridine/tipiracil (FTD/TPI) is used for metastatic colorectal cancer, that is refractory to 5-fluorouracil (5-FU)-based therapies. However, the impact of pre-exposure to 5-FU on the anti-cancer effect of FTD, which is a key component of FTD/TPI, is unclear.. The incorporation into DNA and anti-cancer activity of FTD were analyzed in several cancer cell lines under response to FTD treatment with or without 5-FU pre-exposure. The volumes of tumors in xenografted nude mice were examined among groups that were either untreated or treated with S-1, FTD/TPI or FTD/TPI with pre-exposure to S-1.. Pre-exposure to 5-FU significantly increased FTD incorporation into DNA and enhanced its anti-cancer effect for viability and proliferation of cancer cells. In the xenograft nude mouse model, the tumor volumes in the FTD/TPI-treated and S-1-pre-exposed group were lower than those in the FTD/TPI-only-treated group. Although both FTD dose and exposure time in the FTD/TPI-treated and S-1-pre-exposed mice were smaller than those in the FTD/TPI-only-treated mice, the incorporated FTD in the tumors in the former group was 86.5% of that in the latter group.. Pre-exposure to 5-FU enhanced the incorporation into DNA and the anti-cancer effect of FTD in the context of colorectal cancer. Our data indicate the potential for a new sequential therapy using S-1 and FTD/TPI to improve prognosis of colorectal cancer.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; DNA, Neoplasm; Drug Combinations; Fluorouracil; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Prognosis; Tegafur; Trifluridine; Xenograft Model Antitumor Assays

A 77-year-old man was diagnosed with ascending colon cancer with synchronous liver metastasis. Per our policy we first only performed a right hemicolectomy (pSSN2H2M0, stage IV). We then planned S-1 and oxaliplatin (SOX) plus bevacizumab (Bmab) chemotherapy as a neoadjuvant for the resection of liver metastasis. After 4 courses, enhanced CT and EOB-MRI findings showed the liver tumor had significantly decreased in size with no side effects, and we performed a partial liver resection for the S7 lesion. Postoperatively, histopathological analysis revealed only a fibrotic lesion and no cancerous cells in the resected specimen, indicating that chemotherapy had downgraded the tumor to Grade 3. Adjuvant chemotherapy was not continued owing to the patient's refusal, but no recurrence was noted 18 months after the second operation. SOX plus Bmab chemotherapy is, therefore, effective in terms of its anti-tumor effects, tolerance, and accessibility. We believe SOX plus Bmab chemotherapy can be considered as an effective option for cases with synchronous liver metastasis of colon cancer as neoadjuvant chemotherapy for interval liver resection.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colon, Ascending; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

A 47-year-old woman presented with a hard umbilical nodule that appeared red and was painful. A biopsy of the umbilical nodule revealed adenocarcinoma. As a result of general examinations, the patient was diagnosed with umbilical, hepatic, and ovarian metastases from transverse colon cancer. She was treated with S-1 and oxaliplatin(SOX)plus bevacizumab chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and umbilical and hepatic metastases had reduced in size. We considered this to be a partial response and thus administered 4 additional courses of SOX plus bevacizumab chemotherapy. Finally, she remained well for 22 months and achieved relatively good prognosis. An umbilical metastasis from an internal malignancy is known as a Sister Mary Joseph's nodule, and it has very poor prognosis. Most studies show that the survival period from the time of diagnosis is within 1 year. However, our case suggests that novel anti-cancer drugs or molecular-targeted agents may improve survival.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colon, Transverse; Colonic Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Oxaliplatin; Oxonic Acid; Sister Mary Joseph's Nodule; Tegafur

S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b

Topics: Administration, Intravenous; Animals; CD11b Antigen; Cell Line, Tumor; Colonic Neoplasms; Drug Combinations; Extracellular Vesicles; Humans; Ileum; Lentinan; Membrane Proteins; Mice; Mice, Inbred BALB C; Models, Animal; Oxonic Acid; Tegafur

Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev) is safe and\ feasible for patients with advanced or recurrent colorectal cancer, it is difficult to achieve a complete\ response (CR) using only chemotherapy. A 67-year-old man underwent endoscopic mucosal resection\ and additional sigmoidectomy (D2 dissection) for submucosal invasive sigmoid colon cancer. Multiple\ liver metastases were diagnosed 1.5 years later, and chemotherapy with SOX + bev was initiated.\ Computed tomography (CT) after the end of the third course revealed reduced liver recurrence. Liver\ metastases could not be identified using CT after the end of the sixth course. Grade 1peripheral\ neuropathy was the only side effect of this regimen. Subsequently, the chemotherapy regimen was\ changed to oral S-1. CT evaluation revealed that there was no recurrence at 6 months after the\ regimen change.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Drug Combinations; Humans; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Recurrence; Tegafur

This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Retrospective Studies; Tegafur

The recommended regimen for S-1 internal use is 4 weeks of daily medication and 2 weeks of drug holiday. However, we experience many cases where changing the regimen is ineffective because of adverse events. This time, we report a favorable case of alternate-day treatment with S-1 in an elderly patient with multiple lung metastases of colon cancer. An 84-year-old woman, performance status 2, was diagnosed as having colon cancer and multiple lung metastases. After operation of the colon, she received chemotherapy with the S-1 alternate-day treatment. The lung metastases decreased remarkably, and she was able to continue the treatment without significant adverse events. She has been receiving the treatment without progression for more than 18 months now. The alternate-day treatment with S-1 is reported as a cure with anticancer efficacy and few adverse events. This treatment seems to be a useful chemotherapy for elderly patients with colon cancer.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Tegafur; Treatment Outcome

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Cost-Benefit Analysis; Decision Support Techniques; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Tegafur

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Combinations; Female; Humans; Leucovorin; Male; Oxonic Acid; Tegafur; Uracil

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Combinations; Female; Humans; Leucovorin; Male; Oxonic Acid; Tegafur; Uracil

A 78-year-old woman was diagnosed with liver and para-aortic lymph node metastasis of colorectal cancer via abdominal computed tomography (CT) during a post-operative follow-up. She and her family declined intensive chemotherapy. Therefore, reduced S-1 (80 mg/body/day) was administered for 2 weeks followed by a 2 week interval. After 5 courses, CT revealed a complete response for the liver metastasis and a partial response for the para-aorticlymph node metastasis. Twenty-four courses of chemotherapy were completed, and only a follow-up CT examination was performed. The paraaorticlymph node grew larger, but the liver metastasis did not reappear. Herein, we report a case that showed a good response to S-1.

Topics: Aged; Antimetabolites, Antineoplastic; Aorta; Colonic Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Oxonic Acid; Tegafur; Treatment Outcome

We report a case of adenosquamous carcinoma of the colon. A 70-year-old woman underwent a colonoscopic examination because of a positive fecal occult blood test. Colonoscopy demonstrated a type 2 tumor of the ascending colon, and a biopsy specimen showed poorly-moderately differentiated tubular adenocarcinoma. We performed a right hemicolectomy with D2 lymphadenectomy. The histopathology of the tumor demonstrated adenosquamous adenocarcinoma. Primary adenosquamous carcinoma of the colon is relatively rare and has a poor prognosis. Therefore, adenosquamous carcinoma of the colon may require strict follow-up.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Colectomy; Colon, Ascending; Colonic Neoplasms; Colonoscopy; Drug Combinations; Female; Humans; Oxonic Acid; Tegafur

We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70-year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage Ⅲa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Docetaxel; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer.. Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated.. Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred.. This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer.

Topics: Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Fluorouracil; Humans; Irinotecan; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Treatment Outcome

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asia; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Drug Combinations; ErbB Receptors; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Oxonic Acid; Panitumumab; Practice Guidelines as Topic; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib.. A 70-year-old man had undergone surgery three times for sigmoid colon cancer and recurrence. Systemic chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had already been administered because of metastatic colon cancer. The patient's medical history was CML, and he had been receiving dasatinib treatment (100 mg once daily). Based on the diagnosis of unresectable and multiple metastases, S-1 monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days, followed by a 14-day rest. Blood samples were obtained before and after the first administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a pharmacokinetics study of S-1.. The area under the plasma concentration-time curve (AUC0-8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP, Oxo, and 5-FU after treatment with S-1 were not significantly different from a phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib, CML relapse and serious myelosuppression were not observed.. Our report suggests that S-1 is an important treatment option for recurrent colorectal cancer in patients with CML treated with dasatinib.

Topics: Aged; Antimetabolites, Antineoplastic; Area Under Curve; Colonic Neoplasms; Dasatinib; Drug Combinations; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Protein Kinase Inhibitors; Pyrimidines; Tegafur; Thiazoles

In June 2010, a 67-year-old man presented with advanced gastric cancer. He underwent 2 courses of combination chemo- therapy with S-1/CDDP. After chemotherapy, total gastrectomy was performed (pT4aN3aM0, Stage IIIC). Although he underwent S-1 chemotherapy, colon tumors recurred 22 months after the operation. Colonoscopy revealed the presence of type 2 advanced cancer in the ascending colon, and type IIa early cancer in the transverse colon, which were diagnosed as either primary colon cancers or recurrent gastric cancers upon pathological examination. In October 2012, resection of the right side of the colon was performed in order to prevent malignant bowel obstruction. Pathological examination of the resected specimen identified recurrent gastric cancers. After the surgery, he is currently undergoing S-1 chemotherapy and has no sign of recurrent tumors.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Gastrectomy; Humans; Intestinal Obstruction; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A 55-year-old man suffering from gastric cancer associated with metastases to the lymph node, gallbladder, and liver was administered chemotherapy with S-1 and cisplatin. Before initiation of therapy, the primary tumor, lymph node metastases, and liver metastases showed fluorodeoxyglucose (FDG) accumulation by positron emission tomography (PET). After 1 course of chemotherapy, the patient received curative surgical treatment including distal gastrectomy, partial hepatectomy, cholecystectomy, and lymph node dissection. The final pathological finding was moderately differentiated adenocarcinoma, T4b(SI), N3a(10/20), P0, CY0, pH1, pM1, Stage IV. Five months after surgery, the serum carcinoembryonic antigen (CEA) level was found to be increasing and PET examination identified an FDG-accumulating nodule in the ascending colon. Colonoscopy identified a submucosal tumor diagnosed as a metastasis from the gastric cancer. Right colectomy was performed 7 months after the first surgery resulting in a curative resection. In each surgery, PET examination indicated that no other distant metastases existed, and curative resection would be possible. Furthermore, although solitary metastatic colorectal lesions are rare, PET examination revealed them accurately. Thus, FDG-PET is very useful for identifying metastases in patients with gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

The patient was a 78-year-old woman who suffered from right upper quadrant pain. She was diagnosed as colon cancer with hepatic metastasis. Initial chemotherapy using capecitabine plus oxaliplatin(XELOX)+bevacizumab achieved partial response. After 12 months, XELOX was discontinued due to Grade 3 hand-foot syndrome and peripheral neuropathy. Irinotecan plus oral S-1(a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate)and(IRIS)+bevacizumab were continued as second-line therapy, and her status was maintained as stable disease. XELOX and IRIS regimens do not require catheter placement and long infusion process, providing a great advantage to patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Liver Neoplasms; Oxaloacetates; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 72-year-old woman was diagnosed as Stage IV ascending colon cancer, with metastasis of lung and para-aortic lymph node. She received laparoscopic assisted right hemicolectomy for the local control. After the operation, we performed chemotherapy. We report a case of metastatic ascending colon cancer showing complete response(CR)to 3 courses of S-1/ oxaliplatin(SOX)regimen, and maintaining a CR status while being followed with UFT for 20 months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Combinations; Female; Humans; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Quality of Life; Tegafur; Tomography, X-Ray Computed; Uracil

We recently proposed an S-1 combined with oxaliplatin (SOXL) regimen, a combination treatment consisting of oral metronomic S-1 dosing and intravenous administration of oxaliplatin (l-OHP) containing PEGylated liposomes, which showed potent antitumor activity in vivo. PEGylated liposomes induce what is referred to as the "accelerated blood clearance (ABC) phenomenon" upon repeated administration and consequently lose their long-circulating characteristics. This phenomenon seems to pose an impediment for the clinical application and use of PEGylated liposomal formulations. In the present study, l-OHP-containing PEGylated liposomes in the SOXL regimen significantly attenuated the ABC phenomenon in a dose-dependent manner through suppression of the anti-PEG IgM response, which allowed an enhanced hepatic uptake of subsequently injected test PEGylated liposomes. In tumor-bearing mice, the abrogation of the ABC phenomenon restored intratumor accumulation of subsequently injected PEGylated liposomes. Consequently, the therapeutic efficacy of the SOXL regimen over the combination of the free form of the drugs was credited not only with the selective delivery of drugs to the tumor tissue but also with ensuring an adequate accumulation of subsequent doses within the tumor tissue. The SOXL regimen we proposed may hold promise as a safe and effective treatment regimen for advanced colorectal cancer.

Topics: Administration, Metronomic; Animals; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Drug Delivery Systems; Liposomes; Liver; Male; Mice; Mice, Inbred BALB C; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polyethylene Glycols; Tegafur; Tissue Distribution

To report dacryoendoscopic observations and the incidence of lacrimal obstruction/stenosis associated with S-1, an oral anticancer drug.. Retrospective, nonrandomized clinical trial.. A total of 52 patients (41 men, 11 women; age 42-93 years) who were prescribed the anticancer drug S-1 were studied. Patients who suffered eye complaints following S-1 treatment underwent ophthalmic examination, probing and lacrimal irrigation. Patients whose tear meniscus was high or had abnormal lacrimal irrigation were evaluated by dacryoendoscopy.. Overall, 5 of 52 S-1-treated patients (9.6%) experienced lacrimal passage stenosis/obstruction. One patient had punctal stenosis, and four patients had canalicular obstruction/stenosis. The onset of epiphora ranged from 2 to 8 months (4.4 ± 2.2 months, mean ± SD) after the initiation of chemotherapy.. Patients receiving S-1 treatment should be evaluated for potential lacrimal disorders, particularly canalicular obstruction/stenosis. Dacryoendoscopic observation is effective for the diagnosis of this side effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Combinations; Endoscopy; Female; Humans; Incidence; Lacrimal Duct Obstruction; Lung Neoplasms; Male; Middle Aged; Nasolacrimal Duct; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms; Tegafur

The patient was a 77-year-old woman admitted for nausea and abdominal pain. Computed tomography (CT) revealed advanced ascending colon cancer with liver metastasis. After operation, we started combination chemotherapy of S-1 and irinotecan (CPT-11); S-1(80 mg/m²) administered orally for consecutive days followed by 14 days rest.CPT -11 (100 mg/m²) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent dyspnea with severe hypoxemia after the first course of combination chemotherapy of S-1 and CPT-11.CT scan showed diffuse interstitial lesions with ground glass opacity on both lungs. Steroid pulse therapy with oxygen therapy remarkably improved her symptoms, and abnormal findings on CT scan also resolved. Drug lymphocyte stimulation test was positive against S-1 and negative against CPT-11. These findings were consistent with S-1-induced lung injury. Drug -induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1 and CPT-11 combination therapy present high fever and dyspnea.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Fatal Outcome; Female; Humans; Irinotecan; Lung Diseases, Interstitial; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 69-year-old man was referred to our hospital with the chief complaint of a palpable abdominal mass. Computed tomography and colonofiberscopy revealed that a large type 2 ascending colon cancer had invaded the duodenum and pancreas. To down-size the tumor, chemotherapy was planned and a FOLFOX regimen was effective; we therefore decided to perform a radical operation. The patient is still alive and disease-free 1 year and 8 months after the surgery.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Combinations; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Oxonic Acid; Pancreaticoduodenectomy; Tegafur; Tomography, X-Ray Computed

To evaluate the feasibility of oral fluoropyrimidines after resection and microwave coagulation(MCT), or radiofrequency ablation(RFA)of liver metastases from colorectal cancer.. Background factors, fluoropyrimidine administration(S-1 or UFT/LV), and adverse events were analyzed in 20 patients(17 males, 3 females; an average of 62. 4 years)with colorectal liver metastases after resection and RFA or MCT.. The synchronous: metachronous metastases ratio was 13:7. Fifteen patients received the recommended dose and 5 received a reduced dose. S-1 was administered for 4 weeks followed by a 2-week rest for 7 patients, and for 2 weeks followed by a 1-week rest for 9 patients. UFT/LV was administered for 4 weeks followed by a 1-week rest for 4 patients. Fourteen patients(70%)had adverse events. One patient showed grade 3 leukocyte toxicity while other patients showed grade 1 or 2. Two patients discontinued chemotherapy because of grade 2 delirium and grade 2 CPK elevation; another 2 discontinued voluntarily. Eight patients with recurrence changed the rugs, while 8 of 12(67%)continued for 1 year. Median disease-free and med ian overall survival lengths were 16. 1 and 4 7. 6 months, respectively.. S-1 and UFT /LV were used safely as adjuvant chemotherapies after the resection and local coagulation therapy of liver metastases.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Electrocoagulation; Female; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur; Uracil

A 73-year-old man had undergone right hemicolectomy for advanced colon cancer in May 2006, and he concurrently had multiple liver metastases. After the operation, the patient was given chemotherapy with FOLFIRI. A partial response was achieved for twelve months, and then the liver tumors enlarged. Second-line chemotherapy with FOLFOX was delivered. After several months the liver tumors further enlarged and a new pulmonary lesion appeared with an increased serum CEA level. Therefore, chemotherapy with S-1 (120 mg/day) was started, with 2 weeks' administration followed by a one-week drug-free period. Several months later, the liver tumors and tumor makers decreased. S-1 is expected to be an effective agent for the treatment of advanced colon cancer with liver metastases after FOLFIRI and FOLFOX.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Carcinoembryonic Antigen; Colonic Neoplasms; Drug Combinations; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Oxonic Acid; Salvage Therapy; Tegafur; Tomography, X-Ray Computed

In May 2005, a 79-year-old woman was referred to our hospital with complaints of right lower quadrant mass and feces mixed with blood. After examination, she was diagnosed with ascending colon cancer and synchronous multiple liver metastases. Postoperative diagnosis after right hemicolectomy and D3 lymph node dissection was T2, N1, H2, P0, M0, and Stage IV. One month after the operation, we started a combination chemotherapy using 5-FU plus UFT as pharmacokinetic modulating chemotherapy with hepatic arterial infusion (HAI-PMC). But abdominal CT scan revealed the increase of multiple liver metastases, PD, after 4 courses of treatment. We then changed to modified HAI-PMC (additional CPT-11, once every four weeks), but had to cancel it due to her exhaustion and inappetence. Therefore, S-1 was started from October, 2005. Each course consisted of daily oral administration of 80 mg S-1 for 4 weeks and withdrawal for 2 weeks. After 4 courses, abdominal CT scan revealed a reduction in the number of multiple liver metastases, PR. PR has continued for a long term to date. As an adverse event, we had grade 3 neutropenia and grade 2 diarrhea in January 2009, and we changed the administration method (80 mg S-1 for 2 weeks and withdrawal for 1 week). She continues to undergo outpatient treatment with good QOL without a lesion for 4 years and 6 months. S-1 is expected to be an effective agent for the treatment of advanced colon cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Quality of Life; Tegafur; Time Factors; Tomography, X-Ray Computed

Although lymph node metastasis (LNM) is the most critical prognostic factor in colorectal cancer patients, the anti-LNM efficacy of chemotherapeutic agents is largely unknown because of the limitations of reproducible human colorectal cancer LNM models. Here, we developed a new LNM model from a recently established colorectal cancer cell line (COLM-5) and compared the anti-LNM efficacy of two oral formulations of 5-fluorouracil (5-FU) derivatives, S-1 and UFT/leucovorin (LV). COLM-5 cells is a poorly differentiated adenocarcinoma cell line with unique features such as left-sided, beta-catenin cytoplasmic localization, and microsatellite stable phenotype. COLM-5 cells expressed vascular endothelial growth factor (VEGF-C) and exhibited peritumoral lymphangiogenesis. Consequently, they showed high LNM potential at an incidence of approximately 90% when subcutaneously injected into nude mice, allowing use for preclinical study. When chemotherapy with S-1 or UFT/LV started from the micrometastasis stage, not the advanced macroscopic metastasis stage, anti-LNM efficacy of S-1 was significantly higher than that of UFT/LV at the dosage in which antitumor activity of the two drugs against primary subcutaneous tumor was comparable. COLM-5 cells showed expression pattern of 5-FU metabolizing enzymes such as high dihydropyrimidine dehydrogenase (DPD) and low thymidylate synthase (TS)/orotate phosphoribosyltransferase (OPRT) both in vitro and in vivo. These results suggest that the preferential anti-LNM activity of S-1 compared with UFT/LV against high-DPD COLM-5 tumors is due to the higher DPD inhibitory activity of 5-chloro-2, 4-dihydroxypyrimidine (CDHP) present in S-1 than uracil in UFT. The COLM-5 model would be an excellent tool for understanding the basic mechanism of LNM and for preclinical study on the anti-LNM efficacy of the drugs.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Colonic Neoplasms; Drug Combinations; Drug Evaluation, Preclinical; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Mice; Middle Aged; Oxonic Acid; Tegafur; Uracil; Xenograft Model Antitumor Assays

To clarify the molecular interaction of irinotecan (CPT-11) and oxaliplatin (l-OHP) in combination with 5-fluorouracil (5-FU), the antitumor effects of CPT-11 and l-OHP combined with the oral 5-FU prodrug, S-1 composed by tegafur, gimeracil and potassium oteracil, were investigated on human colon cancer KM12C xenografts sensitive or resistant to 5-FU in nude mice. In parental KM12C tumor xenografts, combined treatment of CPT-11 with oral S-1 significantly augmented the antitumor activity compared with those of CPT-11 and S-1 alone. Interestingly, combined therapy of CPT-11 with S-1 was markedly effective with almost 90% of inhibition of tumor growth on 5-FU-resistant tumors (KM12C/ 5-FU), and its potency likely corresponded to that in parental tumors. In contrast, combined administration of l-OHP with S-1 did not shown an effect on KM12C/5-FU tumor xenografts. To investigate why only CPT-11 potentiated the anti-tumor activity in combination with 5-FU pro-drugs against 5-FU-resistant colon tumors, the activities or expression levels of thymidylate synthase (TS), ribonucleotide reductase (RNR) and other enzymes in 5-FU-metabolism in both tumors were measured following administration of CPT-11 and/or l-OHP. CPT-11, but not l-OHP, induced a decrease in activities and protein levels of TS and an increase in those of RNR in KM12C/5-FU tumors only, which was likely related to decreased expressions of several proteins in G1/S phase of the cells including CDK4, pRB, and E2F1 in these tumors. These findings suggest that CPT-11, but not l-OHP, would overcome the resistance to 5-FU in combination with 5-FU pro-drugs on 5-FU-resistant colon tumors.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Camptothecin; Colonic Neoplasms; Down-Regulation; Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; Humans; Irinotecan; Mice; Mice, Nude; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prodrugs; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

To investigate the usefulness of S-1 for the treatment of peritoneal metastasis from colon cancer using a colon cancer peritoneal metastasis model.. Colon 26 PMF-15 cells were transplanted intraperitoneally into mice. The concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) in the plasma and peritoneal tissue of the mice were determined at 6 sampling time points, i. e., pre-dosing and at 30min, 1, 2, 4 and 8 hrs after oral administration of S-1 (10mg/kg equivalent of FT) on day 20 post-transplantation.. The AUC0-8h values of both 5-FU and CDHP were greater in the peritoneal tumor tissue than in the normal peritoneal tissue. The AUC of 5-FU in the peritoneal tumor tissue was 2. 90 times higher than that in plasma.. The results suggest that S-1 may exert an antitumor effect on peritoneal metastasis arising from colon cancer and be potentially useful as a therapeutic agent in cases of colon cancer with peritoneal metastasis, which is generally recognized as carrying an unfavorable prognosis.

Topics: Administration, Oral; Animals; Cell Line, Tumor; Colonic Neoplasms; Disease Models, Animal; Drug Combinations; Male; Mice; Neoplasm Transplantation; Oxonic Acid; Peritoneal Neoplasms; Tegafur

The aim of this study was to analyze the risk factors for grade 3 to 4 hematological toxicity after primary chemotherapy (Tegafur, gimeracil, oteracil potassium (S-1)/irinotecan hydrochloride (CPT-11)) in 87 (56 male, 31 female; median age 66.1 years) patients with unresectable or recurrent colonic cancer between April 2005 and May 2009, and to prepare a risk classes (low-risk, intermediate-risk or high-risk groups). The rate of grade 3 to 4 hematological toxicity was 16.1%. At multivariate analysis, risk factors for grade 3 to 4 hematological toxicity were baseline WBC, Cr, female (p<0.05). The toxicity index (TI) consisted of risk factors and regression coefficient. We were stratified patients into three groups according to TI that was calculated for each patient. The group with high value was found to include patients with grade 3 to 4 hematological toxicity with a significantly higher frequency than the group with low value (4.2% vs 57.1%, p=0.004). This risk classes could be useful to identify patients at high risk for chemotherapy-induced grade 3 to 4 hematological toxicity.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Hematologic Diseases; Humans; Irinotecan; Male; Neoplasm Recurrence, Local; Oxonic Acid; Risk Factors; Tegafur

We report the case of a 60-year-old woman with multiple lymph node metastases after ascending colon cancer who received radiation therapy and then chemotherapy with S-1. She was diagnosed with lymph node metastasis of the para aorta and left upper clavicle 10 months after surgery. We performed radiation therapy for the left upper clavicle (64 Gy)and para aorta (40 Gy). Consequently, we administered S-1(100mg/day)orally. After three months, the upper clavicle lymph nodes had disappeared and the para-aortic lymph nodes reduced. All metastatic lesions disappeared after 10 months. She survived for 32 months after the radiation therapy.

Topics: Administration, Oral; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Tegafur

The efficacy of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer was studied.. The efficacy of treatment with S-1 (initial dosage: 80 mg/m(2)) was studied in 19 patients with advanced recurrent colon cancer in whom PD was observed after pretreatment with 5-FU-based combination chemotherapy had been performed during the period from December 2003 to April 2006. Patients who underwent a course that exceeded 1 month after the pretreatment and who met the criteria for the appropriate use of S-1 were selected as subjects.. The median age was 65 years (45 to 75 years old) with 10, 6, and 3 patients having a PS score of 0, 1, and 2, respectively, and the details of the duration of the pretreatment was that 12 and 7 patients respectively received 2nd-and 3rd-line therapy. The median duration of the treatment with S-1 was 141 days, and the number of subjects with PR, SD, and PD who underwent S-1 treatment was 2, 7, and 6, respectively, with a response rate of 13. 3% and a disease control rate of 60. 0%. The progression free survival time and the overall median survival time were 5. 4 months and 13. 9 months, respectively. Regarding the effectiveness according to treatment line, particularly in the subjects who were administered S-1 as part of the 2nd-line therapy, good results were observed, thus showing a response rate of 20% and an overall median survival time of 13. 9 months, which exceeded 1 year. The incidence of adverse events was 58%(11 and 19), and the major side effects were neutropenia in 31. 6% (6 and 19) and leukopenia in 21. 1% (4 and 19) of the patients, which are both mild and showed a grade of 2 or lower.. The use of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer may contribute to good prognoses.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Prognosis; Recurrence; Salvage Therapy; Survival Rate; Tegafur

A 78-year-old woman was admitted to our hospital complaining of persistent abdominal pain and diarrhea. Computed tomography (CT) and colonoscopy (CF)revealed a huge ascending colon tumor, invading the descending part of the duodenum. The patient was treated preoperatively with a combination of S-1 plus CPT-11 (S-1 80 mg/body day 1-29, CPT- 11 100 mg/body day 1, 8, 15 and 22). No serious side effect was observed except low-grade fever and grade 2 appetite loss and diarrhea. Tumor reduction was significant on the preoperative CT and CF, with the invasion to the duodenum obscured. Right hemicolectomy with wedge resection of the duodenum was performed. Resected specimen revealed residual tumor in a small area of the submucosal to proper muscular layer of the contracted ascending colon, without pathological invasion to the duodenum. No nodal metastasis was observed. The patient was administered UFT (300 mg daily)postoperatively for two years and is still alive and free of disease after three years and ten months since the operation.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colonic Neoplasms; Colonoscopy; Combined Modality Therapy; Drug Combinations; Female; Humans; Irinotecan; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 45-year-old male patient with right colonic cancer, of which clinical finding was SIM1 (No.216), Stage IV, underwent extended right hemicolectomy with paraaortic lymph node resection as surgical treatment. However, CY1 was detected and a final finding was SIM1 (No.216) H0CY1, Stage IV. After the operation, we administered 3-course of FOLFOX4 plus bevacizumab protocol, 3-course of FOLFOX4, 6-course of FOLFIRI, and 6-course of IRIS for one year. The patient is presently alive with no sign of recurrence after 22 months.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Postoperative Period; Tegafur

A 67-year-old man with multiple liver metastases of colonic cancer was treated with combination therapy of S-1 and irinotecan (CPT-11): S-1 (120 mg/day) administered orally for 14 consecutive days followed by 14 days rest. CPT-11 (100 mg/m(2)) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent exertional dyspnea in the middle of the second course of S-1/CPT-11 therapy. He was hospitalized with severe hypoxemia. CT scan showed extensive ground glass and consolidative changes in bilateral lungs. Steroid pulse therapy with oxygen therapy remarkably improved his symptoms, and abnormal findings on CT scan also resolved. Drug-induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1/CPT-11 combination therapy present high fever and dyspnea.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Diseases, Interstitial; Male; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Failure

We report three cases with liver metastasis from gastric or colon cancer successfully treated with S-1 with CPT-11. Case 1: A total gastrectomy was performed for a gastric cancer located in the lower to upper body of the stomach (T3 (SE), N2, H0, P0, por 2, stage III B). Abdominal computed-tomography (CT) revealed a solitary liver metastasis in the S8 subsegment of the liver. We treated the patient with S-1 combined with CPT-11. Abdominal CT revealed a complete response (CR) after 5 courses. Case 2: Sigmoidectomy and partial resection of small intestine and abdominal wall were performed for sigmoid colon cancer. The intraoperative findings revealed liver metastases in left lobe of the liver (Si, N1, H1, P0, M0, tub 1, stage IV). After surgery, the patient was treated with S-1 combined with CPT-11. Abdominal CT demonstrated CR after 5 courses. Case 3: Laparoscopic right hemicolectomy was performed for ascending colon cancer (SE, N1, H0, P0, M0, tub 1, stage III a). Abdominal CT showed a solitary liver metastasis in the S6 subsegment of the liver 3 months after surgery. We treated the patient with S-1 combined with CPT-11. Abdominal CT revealed CR after 3 courses. The three cases are alive without any signs of recurrence.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to take a malignant course. Most cases are young and early stage, and the surgical strategy is available. But appropriate chemotherapy for inoperable cases with peritoneal dissemination is not established. A 77-year-old woman with a past history of appendectomy was admitted to our hospital complaining of abdominal fullness. Abdominal computed tomography showed massive ascites and slight contrast enhancement of appendix. A tumor was found by colonoscopic examination at the orifice of vermiform and was diagnosed pathologically as goblet cell carcinoid of the appendix. Laparoscopy showed multiple peritoneal dissemination. We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week without any resection of the tumor. Ascites were reduced immediately, but drug-induced interstitial pneumonia occurred due to PTX. After steroid therapy, we switched to systemic S-1 therapy. For about one year, her tumor was controlled but became worse thirteen months after diagnosis and died. It is thought that intraabdominal paclitaxel administration and systemic S-1 therapy can be one of appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from goblet cell carcinoid of appendix.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Colonic Neoplasms; Colonoscopy; Drug Combinations; Female; Humans; Injections, Intraperitoneal; Oxonic Acid; Paclitaxel; Peritonitis; Tegafur; Tomography, X-Ray Computed; Treatment Failure

An 82-year-old female with unresectable colon cancer accompanied by multiple lung metastasis was treated with S-1. Our course consisted of S-1(80 mg/body)from day 1 to 5 followed by 2 days rest. After 14 courses, multiple lung metastasis decreased in size. After 20 courses, the multiple lung metastasis disappeared and local recurrence of colon cancer decreased. Weekly S-1 leads to a partial response. Our chemotherapy showed simple and good compliance for a patient over 80 years old.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Failure

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Pleurisy; Positron-Emission Tomography; Tegafur; Time Factors; Tomography, X-Ray Computed

We report a patient with multiple hepatic metastases and ovarian metastases of transverse colon cancer treated by combination of S-1 and CPT-11. The patient was a 51-year-old woman with cancer of the transverse colon and multiple hepatic metastases. She had undergone surgery. Resection of the transverse colon and left ovary was performed because left ovarian metastases were found during the operation. After the operation, the patient was given chemotherapy with S-1 (120 mg/body on days 1-14) and CPT-11 (150 mg/body on day 1). After completion of 11 courses of chemotherapy, abdominal CT scans revealed that the LDAs of the liver had disappeared, so the patient was judged to have achieved CR. No adverse event was observed. This case suggests that the combination of S-1 and CPT-11 may be an effective regimen for advanced colon cancer with multiple hepatic metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Middle Aged; Ovarian Neoplasms; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

In addition to the direct cytotoxic effects of chemotherapy agents on tumor cells, the anti-angiogenic activities attained by these agents by targeting proliferating endothelial cells in tumor blood vessels has attracted much research interest. In this study, we examined the antitumor activity of 5-Fluorouracil (5-FU)-based drugs (S-1 [1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine and 1M potassium oxonate] and capecitabine) on human colorectal cancer xenografts and evaluated their anti-angiogenic effects. Both drugs showed significant antitumor activities against COL-1 xenografts at a sub-maximum tolerated dose (sub-MTD), which was lower than the maximum tolerated dose (MTD). At the sub-MTD, a significant reduction in the microvessel number and the enhancement of tumor-associated microvessel endothelial cell apoptosis was seen in xenografts treated with S-1. In addition, we found that thrombospondin-1 (TSP-1) expression, known to be a mediator of the anti-angiogenic effects of metronomic chemotherapy, was significantly up-regulated in xenograft tumor tissues and plasma in animals treated with S-1 at a sub-MTD. Capecitabine also showed a trend toward the induction of TSP-1. These results suggest that 5-FU-based drugs inhibit tumor progression through different modes of action, including cytotoxic activity derived from 5-FU and the inhibition of angiogenesis through the induction of TSP-1.

Topics: Angiogenesis Inhibitors; Animals; Capecitabine; Colonic Neoplasms; Deoxycytidine; Drug Combinations; Fluorouracil; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Tegafur; Thrombospondin 1; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

An 85-year-old man, who had undergone right hemicolectomy and partial hepatectomy for caecum cancer with liver metastasis, was diagnosed with recurrent multiple liver metastasis 10 months after surgery. TS-1 administration at a dose of 80 mg/day induced grade 3 anorexia, and after complete recovery from the adverse reaction, it was converted to a low-dose TS-1 administration at 40 mg/day. This treatment reduced the diameter of the liver metastasis and was continued for ten months without any adverse reaction. Pharmacokinetic analysis in this patient on low-dose TS-1 showed that Cmax and AUC of 5-chloro-2,4-dihydroxypyridine (CDHP) were equivalent to the values reported in cancer patients with normal renal function receiving standard-dose administration. TS-1 therapy may provide a safe and effective alternative to chemotherapy for elderly patients with advanced colorectal carcinoma. Pharmacokinetic analysis could be useful for determining the ideal dose of TS-1.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Appendiceal Neoplasms; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Tegafur

A 50-year-old man was admitted because of right lateral abdominal pain, easy fatigue and anemia. An endoscopic examination revealed advanced ascending colon cancer, and abdominal CT scan demonstrated enlarged metastatic lymph nodes of superior mesenteric arterial circumference. The Serum CEA rose considerably. The preoperative diagnosis was cStage IV (SS, N(4), P(0), H(0), M(-)), and right colectomy was performed on March 2, 2005. The metastatic lymph nodes around the superior mesenteric arterial root macroscopically remained. From the 20th postoperative day, we started combination chemotherapy using S-1 plus CPT-11 as one course for three weeks. S-1 (120 mg/body/day) was orally administered for 2 weeks continuously, and CPT-11 (80 mg/m(2)) was done intravenously on day 1 and 8. Serum CEA was normalized in the middle of 3 courses. Moreover, after 13 courses, a complete response (CR) was noted on the follow-up abdominal CT scan. No severe side effect more than grade 2 was observed, there was no interruption of the dosage, and PS was sufficiently maintained kept enough through this combination chemotherapy. The course has been without metastasis, recurrence and a rise of serum CEA now in the 16th postoperative month. S-1/CPT-11 combination chemotherapy is a promising and effective cure for unresectable progressive recurrent colorectal cancer in future.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colon, Ascending; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Lymph Nodes; Lymphatic Metastasis; Male; Mesenteric Artery, Superior; Middle Aged; Oxonic Acid; Remission Induction; Tegafur

The patient was a 59-year-old woman. We performed chemotherapy using S-1 after resection of sigmoid carcinoma because the patient was diagnosed with metastatic lung tumor. The mass was regarded as metastases and reduced in size. We performed pulmonary segmentectomy. Frozen section pathological diagnosis revealed that it was primary lung cancer.

Topics: Colonic Neoplasms; Colonoscopy; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph node metastases. Ileocecal resection was performed palliatively. Since metastasis to cervical vertebrae was detected after the operation, she received radiation therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was started on an outpatient basis (4 weeks administration followed by a 2-week drug-free period). After 4 courses of this chemotherapy, metastases to both para-aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET. Throughout the period of treatment, there was no adverse effect and this treatment has been maintained. In conclusion, this case seems significant from the viewpoint of achieving a partial response to TS-1 and maintaining a high quality of life. Moreover,we identified the presence of TS and DPD using an immunohistochemical staining technique. The primary tumor was positive for DPD stain test and negative for TS stain test. It was suggested that this cancer especially would respond to TS-1 chemotherapy.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Aorta; Cecal Neoplasms; Cervical Vertebrae; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Oxonic Acid; Pyridines; Remission Induction; Spinal Neoplasms; Tegafur

In December 2002, a 67-year-old man underwent right colectomy (stage IIIa, cur B) for cancer of the ascending colon. Chemotherapy with 5'-DFUR and PSK was performed after surgery, but was discontinued due to grade 3 diarrhea. The patient refused treatment with other drugs. An increased CEA level was observed in July 2004, and metastasis of his colon cancer to the liver, lungs, and supraclavicular lymph nodes was confirmed. The patient agreed to resume chemotherapy in December 2004, and received outpatient treatment with CPT-11 (70 mg/m(2) on days 1 and 8) and TS-1 (100 mg/day on days 1-14). There was a significant decrease of tumor markers and a decrease in the size of the metastatic tumors, with these findings being judged as PR. Diarrhea (grade 1) and oral ulceration (grade 2) were observed during treatment. However, these side effects were transient and resolved temporarily without suspending therapy. Although hepatic dysfunction (grade 2) was observed after the completion of cycle No.5, the patient decided to discontinue treatment. CPT-11/TS-1 chemotherapy seems to be useful for maintaining the QOL of patients with metastatic colon cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Quality of Life; Tegafur

We treated a patient with multiple liver metastases arising from colon cancer in whom the metastatic tumors were responsive to treatment with the combination of TS-1 and CPT-11. The patient was a 71-year-old woman with cancer of the ascending colon and metastatic hepatic tumors. She had undergone surgery on July 28, 2004, and abdominal contrast CT scans obtained after discharge from hospital revealed numerous LDA (low-density areas) in both lobes of the liver. The patient was given ambulatory chemotherapy with TS-1 (120 mg/day on days 1-14) and CPT-11 (100 mg/day on days 1 and 8). After completion of 2 courses of chemotherapy, abdominal contrast CT scans revealed that most of the LDAs in both lobes of the liver had disappeared, and the patient was judged to have achieved PR. No adverse reactions were observed except for a slight decrease of WBC, and her chemotherapy is being continued at present. This case suggests that the combination of TS-1 and CPT-11 may be an effective form of chemotherapy for the treatment of colon cancer with multiple hepatic metastases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Oxonic Acid; Remission Induction; Tegafur

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoembryonic Antigen; Colectomy; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur

An intrahepatic arterial injection of CDDP, doxorubicin and 5-FU, followed by 17 courses of oral TS-1 administration (80 mg/day x 14 days, q=28 days), induced a partial response for 9 months after 18 months of stable disease in a 76-year-old male with asynchronous liver metastasis due to ascending colon cancer. TS-1 showed an excellent anticancer effect against colorectal metastatic liver cancers for a long time without loss of QOL or safety.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colectomy; Colonic Neoplasms; Doxorubicin; Drug Administration Routes; Drug Combinations; Fluorouracil; Humans; Injections, Intra-Arterial; Liver Neoplasms; Male; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

Combined chemotherapy consisting of oral TS-1 and low-dose CPT-11 by hepatic arterial infusion is suggested to be a new effective treatment for multiple liver metastases from colorectal cancer. A 53-year-old man was diagnosed with multiple hepatic metastases from advanced colon cancer (Stage IV). The patient underwent partial resection of the colon and catheter insertion into hepatic artery for arterial infusion in November 2003. He was treated with postoperative combination chemotherapy consisting of UFT and low-dose CPT-11. UFT was administered orally at 400 mg/body/day everyday and CPT-11 was injected at 40 mg/body/week for 6 weeks, followed by a 2 weeks rest interval as 1 cycle. In spite of the reduction of metastatic liver tumors after 2 cycles of the chemotherapy, a metastatic pleural tumor appeared. Therefore, we judged the effect of the chemotherapy to be a progressive disease and changed UFT in the regimen to TS-1. TS-1 was administered orally at 80 mg/body/day under a 2-weeks-on and 1-week-off regimen for 3 times. CPT-11 was injected at 40 mg/body/week for 6 weeks, followed by a 3 weeks rest interval as 1 cycle. A stable disease was maintained for 3 months. Outpatient care was possible because no severe events were observed. Tumors showed a reduction rate of 37.4% after the combination therapy. The patient survived for 285 days after the operation.

Topics: Adenocarcinoma; Administration, Oral; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Irinotecan; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

A 61-year-old man was seen at our hospital because he noticed a mass on the left side of his neck. After examinations, he was diagnosed as transverse colon cancer with the left supraclavicular lymph node metastasis and paraaortic lymph node metastases. Rt. hemicolectomy was performed for the transverse colon cancer. At 15 days after operation, TS-1 chemotherapy was started (each treatment course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the left supraclavicular lymph node had shrunk markedly in physical findings. After the second course, both the left supraclavicular lymph node metastasis and paraaortic lymph node metastases had disappeared in CT findings. A complete remission was observed after the second course, and was maintained thereafter. The serum level of CA 19-9 decreased from 62 U/ml under the normal value after the second course, and was kept under this normal value. Leukopenia and eruption (grade 2) were the only observed adverse effects. This patient continues to undergo outpatient treatment with good QOL.

Topics: Antimetabolites, Antineoplastic; Aorta; Biomarkers, Tumor; CA-19-9 Antigen; Clavicle; Colectomy; Colon, Transverse; Colonic Neoplasms; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

A patient is a 35-year-old man. By a diagnosis of descending colon cancer, descending colon ablative operation and D1 lymph node dissection were performed on April 22, 2004. It was P3H0N1SE, Stage IV in perioperative findings. Abdominal CT showed peritoneal dissemination of 1.7 cm at the right under the abdominal wall wound and 1.2 cm in the rectovesical pouch on May 18, 2004. CPT-11 + TS-1 combination chemotherapy was started on June 22nd. In the five weeks of the combination chemotherapy, continuous infusion of CPT-11 (150 mg/body day 1 and 15) was twice administered, and oral administration of TS-1 (120 mg/body/day) was given for 3 weeks (day 1-21). Peritoneal dissemination disappeared after the two-course end, and we judged it as CR. Furthermore, we were certain that we obtained CR after the three course end. The adverse event was only neutropenia of grade 1. The fourth course was not administered, but recurrence has not been observed. Abdominal CT showed no recurrence on March 3, 2005 since the combination chemotherapy ended 6 months ago.

Topics: Administration, Oral; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Male; Neoplasm Seeding; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Tegafur

Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.

Topics: Aged; Antimetabolites, Antineoplastic; beta-Alanine; Cardiovascular Diseases; Colonic Neoplasms; Drug Combinations; Electrocardiography; Fluorouracil; Heart; Humans; Liver Neoplasms; Lung Neoplasms; Male; Oxonic Acid; Tegafur

A 55-year-old man was referred to us after transverse colostomy for intestinal obstruction caused by descending colon cancer with peritoneal dissemination. The colon lesion was palpated as a well-defined hard mass in the left lower abdomen and the disseminated lesion as a hard mass with an unclear border in the right lower abdomen. CEA level was 917 ng/ml at admission. Left hemicolectomy was performed for tumor reduction and TS-1 of 120 mg/day was started 6 days after surgery (4 weeks administration followed by a 2-week rest period). Administration discontinued due to nausea 4 weeks after commencement of the therapy, and restarted as a 2-week administration followed by a 2-week rest period. There has been no adverse reaction since then. Twenty-seven weeks after surgery, CEA level was reduced to 47 ng/ml and peritoneal dissemination was found to have disappeared upon physical examination and computed tomograph. TS-1 is expected to be an effective agent for the treatment of colon cancer with peritoneal dissemination.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Tegafur

A 51-year-old man was hospitalized for evaluation of dysphagia and bloody stool. Gastrointestinal endoscopy showed esophageal cancer invading the gastric fundus. A metastatic lesion was demonstrated in the sigmoid colon. The patient agreed to have concurrent chemoradiotherapy for the primary lesion, followed by additional chemotherapy. The first course included 30 Gy of radiotherapy given over 3 weeks, together with daily oral administration of S-1 (80 mg/m2 per day) for 2 weeks, and a 24-h infusion of cisplatin (70 mg/m2) on day 8. After a second course of chemoradiotherapy, four additional courses of chemotherapy with S-1 and cisplatin were administered, at 4-week intervals. After the additional chemotherapy, gastroscopy and colonoscopy showed disappearance of both the primary and the metastatic lesions. One year after his initial hospitalization, no recurrence of either the primary or the metastatic tumor lesions is evident.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Humans; Infusions, Intravenous; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). In this study the combined effect of S-1 and low-dose CDDP as a modulator for colon 26 liver metastasis in mice was evaluated. In an experiment with S-1 (5 mg/kg/day: po) and CDDP (0.25 mg/kg/day: i.p.) for 14 days, the combined effects for both liver metastasis and tumor of spleen were not superior to those with S-1 or CDDP alone group. Body weight loss was not greater in the S-1 + CDDP group than in the control group. In an experiment with S-1 (5 mg x 2/kg/day: po) and CDDP (0.25 mg/kg/day: i.p.) for 7 days, the inhibitory effects of S-1 + CDDP of liver metastasis and tumor of the spleen were remarkable compared with the S-1 alone group. However a greater loss of body weight was seen in the S-1 + CDDP group than in other groups. This study suggests that low-dose CDDP might be a modulator of S-1 for colon 26 liver metastasis. Further study is needed to determine the optimum dose and duration of treatment.

Topics: Animals; Antimetabolites, Antineoplastic; Body Weight; Cisplatin; Colonic Neoplasms; Drug Combinations; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Oxonic Acid; Pyridines; Splenic Neoplasms; Tegafur

S-1 [1 M tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypyridine (CDHP)-1 M potassium oxonate (Oxo)], was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CDHP and Oxo. The therapeutic effect of S-1 on human colon cancer xenografts (TK-13) with high metastatic potential to the liver was evaluated. Small pieces of TK-13 were sutured into the cecal wall of 52 nude mice, and the animals were randomly divided into 3 groups [control (n=17), UFT (combination of 1 M FT and 4 M uracil) (n=18) and S-1 (n=17)]. S-1 or UFT was administered orally at an equitoxic dose (S-1, 7.5 mg/kg; UFT, 17.5 mg/kg as FT) for 37 consecutive days beginning 10 days after the transplantation. S-1 showed higher tumor growth inhibition than UFT (P<0.05) and also showed a significant anti-metastatic effect on liver metastasis, while UFT did not. Liver metastasis developed in only 2 of the 17 mice (12%) in the S-1 group, whereas it developed in 9 of the 17 (53%) and 7 of the 18 (39%) in the control and UFT group, respectively. Analysis of AUC (area under the curve) revealed that S-1 yielded higher 5-FU levels in both tumor tissue (1.6 times) and plasma (2.5 times) than UFT. These results suggest that S-1 will show a higher clinical therapeutic effect against human colorectal cancer than UFT.

Topics: Animals; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Combinations; Humans; Liver Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Oxonic Acid; Pyridines; Tegafur; Transplantation, Heterologous

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Colonic Neoplasms; Drug Combinations; Fluorouracil; Humans; Neoplasm Metastasis; Neoplasm Transplantation; Oxonic Acid; Prodrugs; Pyridines; Rats; Rats, Nude; RNA; Tegafur; Transplantation, Heterologous