Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

Abstract

BACKGROUND Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5‐fluorouracil (5‐FU), and cisplatin in the treatment of patients with advanced gastric carcinoma. METHODS Forty‐one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3‐hour intravenous (i.v.) infusion on Day 1, 5‐FU 750 mg/m2 by 24‐hour continuous i.v. infusion on Days 1–5, and cisplatin 20 mg/m2 by 2‐hour i.v. infusion on Days 1–5. Twenty‐six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity. RESULTS Twenty‐one of the 41 patients (51%; 95% confidence interval [CI], 36.5–65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9–22.5%). Sixty‐five percent of the patients with measurable disease (17of 26; 95% CI, 58–92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1–52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4–90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred. CONCLUSIONS Paclitaxel, 5‐FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting. Cancer 1999;85:295–301. © 1999 American Cancer Society.

A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

“…An objective response rate of 51% -or 58% if only those patients receiving at least one complete cycle of therapy are taken into accountincluding 11% (13%) complete remissions in chemonaive gastric cancer patients demonstrates the high activity of this regimen. A similar favourable response rate of 51% with a median survival time of 6 months was recently achieved by Kim et al (1999) administering paclitaxel at a dose of 175 mg/m 2 on day 1, 5-FU at a dose of 750 mg/m 2 on days 1-5 as continuous infusion and cisplatin at a dose of 20 mg/m 2 as a 30 minute infusion on days 1-5. In patients with adenocarcinoma of the oesophagus, Ilson et al (1998) reported a response rate of 46% with a similar schedule.…”

Docetaxel versus Paclitaxel Combined with 5-FU and Leucovorin in Advanced Gastric Cancer: Combined Analysis of Two Phase II Trials

“…This impedes the long-term treatment (3). Therefore, the development of anti-cancer treatments by which the toxicity can be lowered and the quality of life can be improved has been continually made (1).…”

“…For instance, Thus-Patience et al proposed that a single use of DF except for cisplatin had an equivalent profile of the efficacy to epirubicin + cisplatin +5-FU (ECF) or DCF (2). According to various types of Phase II studies, a combination treatment with Paclitaxel produced a response rate of 32�66% and a survival period of 6�12 months (3)(4)(5). To date, however, almost no randomized clinical trials have been attempted to compare the efficacy of these regimen.…”

Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer

“…In our previous study, the paclitaxel and 5-FP combination produced a 51% objective response, which suggests that taxane is efficacious in gastric cancer (Kim et al, 1999). Docetaxel, a semi-synthetic analogue of paclitaxel, was reported to offer superior response rates and a longer time to progression when added to the FP regimen (5-FU/cisplatin) than FP alone in a randomised phase III trial .…”