s-1-(combination) and Linitis-Plastica

We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer.. Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80-120 mg/body, p.o., days 1-21) and cisplatin (CDDP; 60 mg/m(2), i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD).. Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7-81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively.. Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Linitis Plastica; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Stomach Ulcer; Tegafur; Treatment Outcome

Gastric linitis plastica (LP) is usually found as an advanced gastric cancer and has a poor prognosis. No sufficiently effective chemotherapy has been reported. In recent years, TS-1 has yielded a high response rate for advanced gastric cancers and favorable treatment results have also been suggested for gastric LP. We retrospectively compared and discussed anti-tumor effects and survival time for 62 consecutive patients with unresectable gastric LP who underwent chemotherapy at Kitasato University East Hospital between November 1995 and December 2002. They were divided into two groups: 19 patients given chemotherapy including TS-1 as first-line therapy (TS-1 group), and 43 patients given chemotherapy mainly with 5-fluorouracil, cisplatin, methotrexate and mitomycin C (non-TS-1 group). The overall response was 57.9% [95% confidence interval (CI) 35.7-80.1%] in the TS-1 group, which was significantly greater than the 27.9% (95% CI 14.5-41.3%) of the non-TS-1 group (P < 0.01). The median survival time was 402 days (95% CI 251-553 days) in the TS-1 group, which was also significantly longer than the non-TS-1 group (213 days, 95% CI 165-261 days, P < 0.01). Neutropenia and febrile neutropenia of grade 3 or higher were observed in 21.1 and 5.2%, respectively, in the TS-1 group, which were lower than the values of 37.2 and 20.9% in the non-TS-1 group. We conclude that greater anti-tumor effects and longer survival time can be expected from chemotherapy including TS-1 for gastric LP compared with conventional chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Linitis Plastica; Male; Methotrexate; Middle Aged; Mitomycin; Oxonic Acid; Pyridines; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur