Ca-channel blocker-induced gingival overgrowth that improved with non-surgical therapy during visiting care: a case report.

OBJECTIVES: To present a case of gingival overgrowth during visiting care. BACKGROUND: Ca-channel blocker-induced gingival overgrowth is a well-known adverse event. However, only limited information on the treatment of calcium-channel blocker-induced gingival overgrowth during visiting care has been reported. CLINICAL REPORT: The patient was an 88-year-old female living in a nursing home since dementia. She had been taking a calcium-channel blocker and observed gingival overgrowth. Initial therapy was performed and changed the antihypertensive medication from a calcium-channel blocker to an angiotensin converting enzyme inhibitor. After initial therapy, the gingival overgrowth improved significantly. In addition, the defecation rate was improved. CONCLUSION: This case indicated that periodontal therapy is useful even for dementia patients during visiting dental care.

Efficacy and safety of capecitabine plus cisplatin in Japanese patients with advanced or metastatic gastric cancer: subset analyses of the AVAGAST study and the ToGA study.

BACKGROUND: Capecitabine plus cisplatin (XP) is recognized as one of the global standard first-line chemotherapy regimens for patients with metastatic gastric cancer (mGC). Recent multinational phase III trials in mGC have been conducted with XP as the control arm, although no data on XP in Japanese patients with mGC have been published to date. The AVAGAST (XP ± bevacizumab in mGC) and ToGA (XP ± trastuzumab in human epidermal growth factor receptor 2 [HER2]-positive mGC) studies were the first two global studies including Japanese mGC patients. The aim of this analysis was to investigate the efficacy and safety of XP in Japanese mGC patients, using AVAGAST and ToGA subgroup data. METHODS: Efficacy and safety analyses were carried out in Japanese patients with mGC receiving XP alone, based on results from the AVAGAST and ToGA studies. There were differences in the target populations between the two studies; for example, the ToGA study limited patients to those with HER2-positive tumors; therefore, efficacy was evaluated separately. RESULTS: Ninety-four Japanese patients in the AVAGAST study and 50 in the ToGA study received XP alone. Median overall and progression-free survivals were 14.2 and 5.7 months, respectively, in the AVAGAST study, and 17.7 and 5.6 months, respectively, in the ToGA study. Overall response rates were 49.2 % in the AVAGAST and 58.5 % in the ToGA study. Adverse events were generally mild; the most common grade 3/4 events were neutropenia, anemia, anorexia, and nausea. CONCLUSIONS: XP is effective and well tolerated in Japanese patients with mGC, and could be one of the standard regimens for the first-line treatment in this cohort.

A phase I study of triplet combination chemotherapy of paclitaxel, cisplatin and S-1 in patients with advanced gastric cancer.

OBJECTIVE: S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy. METHODS: Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle. RESULTS: Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%. CONCLUSIONS: The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.

[Serotonin syndrome in a patient with small cell lung cancer].

The patient was a 67-year-old male who had been treated for several years with 150 mg fluvoxamine maleate due to depression. He visited our hospital with primary symptoms of swelling of the right upper extremity and dyspnea in August, XXXX. As a result of examinations, he was diagnosed with stage IIIB extended small cell lung cancer(T4N3M0). One course of carboplatin/etoposide(CBDCA/VP-16)therapy was started on October 1. Since the tumor size was reduced, thoracic effusion disappeared, and superior vena cava syndrome was alleviated, the therapy was changed to cisplatin/irinotecan (CDDP/CPT-11)on October 23, and the 3rd course was initiated on November 22. Anxiety and tremor appeared on the 4th day of the 3rd course and because they were exacerbated, and myoclonus appeared, a diagnosis of serotonin syndrome was made on the 38th day, and the administration of fluvoxamine maleate was discontinued. The symptoms were alleviated after the discontinuation, and the 4th course could be implemented. In this patient, serotonin syndrome was considered to have been induced by serotonin secretion promoted by the CDDP administration, and by serotonin in the brain increasing abnormally due to the SSRI.

A multicenter phase II study of the stop-and-go modified FOLFOX6 with bevacizumab for first-line treatment of patients with metastatic colorectal cancer.

Currently, no prospective data exists to support a "stop-and-go" modified FOLFOX6 regimen with bevacizumab in metastatic colorectal cancer (mCRC) patients. This study aimed to evaluate the efficacy and safety of this regimen in first-line mCRC patients. Eligible patients (age ≥20 years) had previously untreated mCRC; Eastern Cooperative Oncology Group performance status of 0-2; and adequate hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8 cycles, patients received maintenance therapy with simplified LV5FU2 and bevacizumab until completion of 8 cycles or disease progression. After maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with bevacizumab until completion of 8 cycles or disease progression. We recruited 50 patients between August 2007 and January 2009. The overall response rate was 48% (80% confidence interval [CI]; 38.2-58) with outcomes as follows: complete response, n = 1; partial response, n = 23; stable disease, n = 21; progression, n = 1; and not evaluated, n = 4. Median time to treatment failure was 7.7 months (80% CI: 6.2-8.0), and median progression-free survival was 12.8 months (80% CI: 10.8-14). Grade 3/4 toxicities included neutropenia (40%), nausea (4%), diarrhea (14%), thrombosis (4%), and hypertension (4%) et al. Grade 1, 2, or 3 peripheral neuropathy was reported in 38%, 40%, and 10% of patients, respectively. The stop-and-go modified FOLFOX6 and bevacizumab regimen is effective and well tolerated as first-line chemotherapy for mCRC patients.

Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study.

BACKGROUND: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2) positive advanced/metastatic gastric or gastroesophageal junction cancer. ToGA showed that trastuzumab plus chemotherapy (capecitabine/cisplatin or 5-fluorouracil/cisplatin) improved overall survival in the overall population (hazard ratio 0.74). Regional differences in outcome in favor of Japanese populations were observed in other studies; therefore, subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients. METHODS: We performed subgroup analyses on 101 Japanese patients enrolled into ToGA (trastuzumab plus chemotherapy, n = 51; chemotherapy, n = 50). RESULTS: Median overall survival in the Japanese subgroup was 15.9 months (95% confidence interval 12-25) for trastuzumab plus chemotherapy and 17.7 months (95% confidence interval 12-24) for chemotherapy (hazard ratio 1.00; 95% confidence interval 0.59-1.69). After adjusting for prespecified covariates, the estimated hazard ratio for overall survival was 0.68 (95% confidence interval 0.36-1.27). Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios. CONCLUSIONS: After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer.

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms in women and the third largest number in men. Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2010.

Application of electrolysis for detoxification of an antineoplastic in urine.

Antineoplastics in excreta from patients have been considered to be one of the origins of cytotoxic, carcinogenic, teratogenic, and mutagenic contaminants in surface water. Recent studies have demonstrated that antineoplastics in clinical wastewater can be detoxified by electrolysis. In this study, to develop a method for the detoxification of antineoplastics in excreta, methotrexate solution in the presence of human urine was electrolyzed and evaluated. We found that urine inhibits detoxification by electrolysis; however, this inhibition decreased by diluting urine. In urine samples, the concentrations of active chlorine generated by anodic oxidation from 0.9% NaCl solution for inactivation of antineoplastics increased in dilution-dependent and time-dependent manner. These results indicate that electrolysis with platinum-based iridium oxide composite electrode is a possible method for the detoxification of a certain antineoplastic in urine.

[Comparison of chemotherapy side effects between elderly and young subjects].

UNLABELLED: With the aging of society, the number of elderly patients receiving chemotherapy has increased. Since organ function, particularly the liver and kidney function, is known to decrease with age, there is concern that severe side effects may develop in the elderly because of chemotherapy. It is a considerable challenge to establish safe, effective chemotherapy that enables elderly patients to maintain a favorable QOL. Therefore, we conducted a survey of the current status of chemotherapy side effects. METHODS: The subjects were patients enrolled in physician-led clinical trials between April 2006 and December 2010. A survey of the chemotherapy regimens used, PS, and, side effects(CTC-AE v3.0)was conducted to examine differences in the incidence and Grade of side effects between elderly and younger subjects(aged 65 years or older, and younger than 65 years, respectively). The subjects consisted of9 3 elderly and younger people, with mean ages of 70 and 59. 5 years, respectively. Myelosuppression of Grade 3, or more severe side effects in the elderly and younger subjects, was 22. 5% and 16. 3%, respectively. The incidence of side effects was slightly higher in the elderly than in the younger subjects. In general clinical practice, side effects are controlled by selecting regimens and adjusting doses for the elderly. However, in clinical trials in which the dosage is predetermined regardless of age, the elderly are more prone to develop side effects than young people. We compare and present the current status regarding the side effects, effectiveness, and contents of chemotherapy regimens.

Second-line chemotherapy for gastric cancer: a new issue lies ahead in global trials.

Chemotherapy for gastric cancer has been advancing fairly well. It has been indicated that not only advances in first-line chemotherapy but also those in second-line chemotherapy have contributed to the prolongation of overall survival. The Arbeitsgemeinschaft Internistische Onkologie (AIO) study supports the idea that second-line chemotherapy is appropriate in patients with a good general condition. Also, the Japan Clinical Oncology Group (JCOG) integral analysis suggests that advances have been made in second-line chemotherapy. However, most recently reported studies of second-line chemotherapy have been conducted as small-scale phase II or retrospective trials. No randomized control trial to establish standard treatment has been reported. Which regimen is the most appropriate as second-line therapy must be investigated in the future. Currently, molecularly targeted agents for gastric cancer are being developed and tested in global trials. As a new issue in global trials, second-line chemotherapy has been emphasized. In recent global trials, subset analysis showed regional differences in overall survival. This was possibly associated with the regional differences in second-line chemotherapy. When developing new molecularly targeted agents for first-line chemotherapy, we cannot ignore the result that the proportion of patients in whom treatment was switched to second-line chemotherapy was high in Asia. In planning a global trial, this new issue should be sufficiently discussed.

A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial).

BACKGROUND: Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer. METHODS: Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR. RESULTS: Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively. CONCLUSIONS: Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.

[Chemotherapy for gastrointestinal cancer in elderly patients].

Since elderly people have decreased renal function along with increased risks for complications of cardiac disorders such as hypertension and decreased physical strength, compared to in younger people, drug therapy for them is associated more with concern about drug-related toxicity. Therefore, dose reduction or discontinuation of drug administration is sometimes considered during earlier stages of therapy. On the other hand, there are some reports suggesting that as long as proper organ function is maintained, the elderly can be treated in the same way as younger people. However, given limited information and depending on the therapeutic goal of each patient, it should be carefully considered whether the same medicinal strategy used for younger patients is appropriate for treating elderly patients or not.

[Phase I / II study of XELOX plus bevacizumab in Japanese patients with metastatic colorectal cancer(JO19380)].

FOLFOX plus Bevacizumab (BEV) is one of he current standard treatments for unresectable colorectal cancer. In Europe and the United States, XELOX is a regimen which replaced 5-FU/LV of FOLFOX with capecitabine (XEL), an oral prodrug of fluorouracil. Benefits of XELOX and FOLFOX are reported to be same in Europe and United States. XELOX + BEV is recommended as treatment option in various guidelines. However, the safety and effectiveness data were from overseas and unconfirmed in Japan. Therefore, we carried out a JO19380 study to evaluate the effectiveness and safety XELOX + BEV on Japanese patients in a domestic phase I/II clinical trial. A total of 64 patients were registered in this study. The response rate was 72%, the progression free survival was 11 months, and the median survival time was 27.4 months with XELOX + BEV. The common grade 3/4 toxicities were sensory neurotoxicity (17%) and neutropenia (16%). The effectiveness and safety equivalents of overseas reports were confirmed in Japanese patients. They suggested that XELOX + BEV has the potential to become one of the standard treatments for unresectable colorectal cancer in Japan. In the trial, long-term disease control with XEL-BEV was reported in patients who discontinued oxaliplatin because of adverse events. Continuous treatment with XEL + BEV after XELOX + BEV is considered to be significant first-line therapy for colorectal cancer based on that report.

Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study).

BACKGROUND: Fluorouracil and folinic acid with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are widely used as first-line or second-line chemotherapy for metastatic colorectal cancer. However, infusional fluorouracil-based regimens, requiring continuous infusion and implantation of an intravenous port system, are inconvenient. We therefore planned an open-label randomised controlled trial to verify the non-inferiority of irinotecan plus oral S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate; IRIS) to FOLFIRI as second-line chemotherapy for metastatic colorectal cancer. METHODS: Between Jan 30, 2006, and Jan 29, 2008, 426 patients with metastatic colorectal cancer needing second-line chemotherapy from 40 institutions in Japan were randomly assigned by a computer-based minimisation method to receive either FOLFIRI (n=213) or IRIS (n=213). In the FOLFIRI group, patients received folinic acid (200 mg/m(2)) and irinotecan (150 mg/m(2)) and then a bolus injection of fluorouracil (400 mg/m(2)) on day 1 and a continuous infusion of fluorouracil (2400 mg/m(2)) over 46 h, repeated every 2 weeks. In the IRIS group, patients received irinotecan (125 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was progression-free survival, with a non-inferiority margin of 1.333. Statistical analysis was on the basis of initially randomised participants. This study is registered with ClinicalTrials.gov, number NCT00284258. FINDINGS: All randomised patients were included in the primary analysis. After a median follow-up of 12.9 months (IQR 11.5-18.2), median progression-free survival was 5.1 months in the FOLFIRI group and 5.8 months in the IRIS group (hazard ratio 1.077, 95% CI 0.879-1.319, non-inferiority test p=0.039). The most common grade three or four adverse drug reactions were neutropenia (110 [52.1%] of 211 patients in the FOLFIRI group and 76 [36.2%] of 210 patients in the IRIS group; p=0.0012), leucopenia (33 [15.6%] in the FOLFIRI group and 38 [18.1%] in the IRIS group; p=0.5178), and diarrhoea (ten [4.7%] in the FOLFIRI group and 43 [20.5%] in the IRIS group; p<0.0001). One treatment-related death from hypotension due to shock was reported in the FOLFIRI group within 28 days after the end of treatment; no treatment-related deaths were reported in the IRIS group. INTERPRETATION: Progression-free survival with IRIS is not inferior to that with FOLFIRI in patients receiving second-line chemotherapy for metastatic colorectal cancer. Treatment with IRIS could be an additional therapeutic option for second-line chemotherapy in metastatic colorectal cancer. FUNDING: Taiho Pharmaceutical Co Ltd and Daiichi Sankyo Co Ltd.

Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer.

OBJECTIVE: The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer. METHODS: Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) on day 1, plus capecitabine 1000 mg/m(2) twice daily on days 1-14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate. RESULTS: No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72% (95% confidence interval, 58.5-83.0). Median progression-free survival was 11.0 months (95% confidence interval, 9.6-12.5) and median overall survival was 27.4 months (95% confidence interval, 22.0-not calculated). Eight patients (14%) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17%) and neutropenia (16%). CONCLUSIONS: XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for pre-treated metastatic colorectal cancer harboring wild-type KRAS.

Standard weekly cetuximab and irinotecan is an effective regimen in heavily pre-treated patients with metastatic colorectal cancer. The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pre-treated metastatic colorectal cancer harboring wild-type KRAS. A total of 30 patients will be enrolled at four medical institutions. The primary endpoint is response rate. The secondary endpoints include adverse events, progression-free survival and overall survival. The pharmacokinetics of cetuximab will also be evaluated in five patients.

[A resected case of effective treatment with S-1+CPT-11 combination chemotherapy for advanced gastric cancer].

We report a resected case of effective treatment with S-1+CPT-11 combination chemotherapy for advanced gastric cancer. The patient was a 65-year-old man who had a type 3 gastric cancer from the middle body of the stomach to the angle. An abdominal CT scan demonstrated bulky lymph node metastasis (cType 3, T3, N2, M0, cStage IIIb), which was then treated with S-1+CPT-11 (S-1 80 mg/m2 day 1-21, CPT-11 80 mg/m2 day 1, 15/5 weeksx2 courses)as neoadjuvant chemotherapy. After 2 courses of chemotherapy, the primary lesion and regional metastatic lymph nodes were reduced by CT (cType 3, T2, N2, M0, cStage IIIa). Total gastrectomy with D3 nodal dissection was performed. The histological diagnosis was pT2 (ss), pN0, sH0, pCY0, sP0, sM0, tub2, INF beta, ly0, v1, n0, stage I b, Cur A, and the histological effect of the main tumor was judged to be Grade 1b. He was treated by S-1 after surgery. The patient has been in good health without a recurrence for 3 years after surgery. This case suggests that neoadjuvant chemotherapy with S-1+CPT-11 is a potential regimen for advanced gastric cancer.

[Combination of S-1 and paclitaxel for advanced/recurrent gastric cancer patients with peritoneal metastasis, feasibility study (OGSG0401)].

BACKGROUND: The standard therapy for gastric cancer with peritoneal metastasis has remained unclear. PURPOSE: This prospective feasibility study was aimed to investigate the efficacy and safety of S-1 plus paclitaxel for advanced/recurrent gastric cancer patients with peritoneal metastasis able to take oral feeding. PATIENTS AND METHODS: Seven patients were enrolled in this study. Paclitaxel 50mg/m2 was administered on days 1 and 8. S-1 was administered orally at 40 mg/m2 bid for 14 consecutive days, followed by a 1-week rest. Overall survival, the response rate and safety were examined for efficacy and tolerability. RESULTS: The median survival time was 310 days. The response rate in five patients was 80. 0%. Grade 3 toxicity was observed in two patients. Combination chemotherapy of weekly paclitaxel and S-1 demonstrated efficacy and tolerable toxicity. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer with peritoneal metastasis.

[Current status and perspectives of biologics in the treatment of metastatic colorectal cancer].

Since the mid 1990s, colorectal cancer treatment has undergone substantial changes and improvements. Combination chemotherapy in first-line treatment of metastatic colorectal disease is the standard of care. Regimens based on either irinotecan or oxaliplatin given with 5-fluorouracil are prevailing. Recently, bevacizumab has become the routine standard addition to FOLFOX in first-line regimens in Japan. This preference is based on the data from NO16966 study, which resulted in a far less substantial improvement in progression free survival and no benefit in response rate. Other clinical trials indicated that the addition of the anti-EGFR monoclonal antibody confers modest benefit to FOLFOX or FOLFIRI. At present, how to combine the available agents and what the ideal combinations should be remain unclear.

Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study.

BACKGROUND: The best chemotherapy regimen for metastatic gastric cancer is uncertain, but promising findings have been reported with irinotecan plus cisplatin and S-1 (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate). We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer. METHODS: We undertook a phase 3 open label randomised trial in 34 institutions in Japan. We enrolled patients aged 20-75 years or younger, who had histologically proven gastric adenocarcinoma, and randomly assigned them by minimisation to receive either: a continuous infusion of fluorouracil (800 mg/m(2) per day, on days 1-5) every 4 weeks (n=234); intravenous irinotecan (70 mg/m(2), on days 1 and 15) and cisplatin (80 mg/m(2), on day 1) every 4 weeks (n=236); or oral S-1 (40 mg/m(2), twice a day, on days 1-28) every 6 weeks (n=234). The primary endpoint was overall survival. Analyses were done by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00142350, and with UMIN-CTR, number C000000062. FINDINGS: All randomised patients were included in the primary analysis. Median overall survival was 10.8 months (IQR 5.7-17.8) for individuals assigned fluorouracil, 12.3 months (8.1-19.5) for those allocated irinotecan plus cisplatin (hazard ratio 0.85 [95% CI 0.70-1.04]; p=0.0552), and 11.4 months (6.4-21.3) for those assigned S-1 (0.83 [0.68-1.01]; p=0.0005 for non-inferiority). Three treatment-related deaths occurred in the irinotecan plus cisplatin group and one was recorded in the S-1 group. INTERPRETATION: S-1 is non-inferior to fluorouracil and, in view of the convenience of an oral administration, could replace intravenous fluorouracil for treatment of unresectable or recurrent gastric cancer, at least in Asia. Irinotecan plus cisplatin is not superior to fluorouracil in this setting.