Phase II Trial of the Combination of Paclitaxel and 5-Fluorouracil in the Treatment of Advanced Gastric Cancer

Abstract

This prospective phase II clinical trial was performed to explore the activity and efficacy of the combination of paclitaxel and 5-fluorouracil in the treatment of advanced gastric adenocarcinoma. Thirty-one patients ages 18 to 70 years, with Karnofsky performance status (KPS) >50, adequate cardiac, renal, and hepatic functions, measurable metastatic or locally unresectable disease, life expectancy > or =3 months, signed written informed consent, and without any previous chemotherapy were assigned to receive on an outpatient basis: paclitaxel--175 mg/m2, in a 3-hour infusion on day 1 and 5-fluorouracil--1.5 g/m2, also in a 3-hour infusion on day 2 every 21 days, for a maximum of seven cycles. A system to assess clinical benefit based on KPS, analgesic consumption, and weight gain was also used in this trial. Median age was 61 years (range, 31-70 years). The 29 patients eligible for response and toxicity evaluation underwent 147 cycles of chemotherapy. There were 19 (65.5%) objective responses (95% confidence interval: 48%-83%), including 7 (24.1%) complete responses and 12 (41.4%) partial responses. Three patients had the complete response pathologically confirmed. In three of six patients who went to second-look laparotomy, a potentially curative esophagogastrectomy was possible. The toxicity of this combination was considered low, predictable, and manageable and was characterized mainly by reversible alopecia, peripheral neuropathy, myalgia, and mild neutropenia. Fifteen (51.7%) patients attained a clinical benefit response. The median overall survival was 12 months (range, 2-30+ months) and the 30-month overall survival was 20%. This novel regimen appears to be very effective in advanced gastric cancer. The projected 2-year survival of 20% is higher than that achieved with other first-line regimens. These encouraging results indicate the need for further studies to confirm the merit of this regimen.

Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy in patients with advanced gastric cancer

“…Because paclitaxel has synergistic antitumor effects with 5-FU, according to clinical trials as well as preclinical studies, and it has a different spectrum of side effects from that of S-1, a combination of paclitaxel and S-1, one of the most potent fl uorinated pyrimidines, was considered to be promising for the treatment of gastric cancer [26,27]. Several clinical trials of S-1 and paclitaxel combination therapy have been conducted in Japan [28][29][30][31][32][33].…”

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for patients with advanced or recurrent unresectable gastric cancer

“…The side eVects include neutropenia, peripheral neuropathy and arthralgia [1]. Paclitaxel has synergistic antitumor eVects with 5-Xuorouracil (5-FU) according to clinical trials as well as preclinical studies, and a diVerent spectrum of side eVects [12,18]. Several clinical trials of S-1 and paclitaxel combination therapy have been conducted in Japan [6,7,9,13,17,20,23].…”

Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer

“…The continuing lack of substantial progress in the treatment of advanced gastric cancer, particularly in patients with poor performance status or compromised organ function, who are unlikely to tolerate potentially active but toxic regimens, has prompted investigators to evaluate new agents and/or drug combinations including docetaxel, paclitaxel, and irinotecan (Bokemeyer et al, 1997;Boku et al, 1999;Murad et al, 1999;Kollmannsberger et al, 2000;Roth et al, 2000;Ridwelski et al, 2001). …”

“…It has demonstrated broad clinical activity in a variety of malignancies both alone and in combination regimens. Antitumour activity of paclitaxel also has been shown in gastric cancer cell lines and in several phase I/II trials (Arbuck, 1994;Bokemeyer et al, 1997;Murad et al, 1999;Kollmannsberger et al, 2000;Safran et al, 2000). Paclitaxel is usually well tolerated with myelosuppression being the dose-limiting toxicity and patients receiving this agent can be treated on an outpatient basis.…”