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

Abstract

SummaryTo evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m 2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m 2 as a 2 h infusion. Paclitaxel 175 mg/m 2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m 2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% Cl: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III°/IV°occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III°/IV°toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

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

“…An administration schedule at doses of 175-225 mg/m 2 by intravenous infusion every 3 weeks has been widely accepted [9]. In addition, several phase II studies have shown that paclitaxel, alone or in combination with cisplatin or 5-fl uorouracil (5-FU), is also active against advanced gastric cancer [10][11][12][13]. However, a relatively high incidence of grade 3 or 4 neutropenia (14%-35%) is one of the major adverse effects.…”

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: A low cost effective regimen

“…Preliminary data on docetaxel (at a dose of 85 mg m 72 ) combined with CDDP every 3 weeks seem to be promising with a response rate of 56% (Roth et al, 2000). Similarly, Kollmannsberger et al (2000) reported a response rate of 51% combining paclitaxel with CDDP and 5-FU. However, the results obtained with these newer schedules seem to be comparable with those of our regimen.…”

“…New cytotoxic agents, such as irinotecan, paclitaxel and docetaxel could be a more appealing approach for the treatment of advanced gastric cancer (Kollmannsberger et al, 2000;Mavroudis et al, 2000;Roth et al, 2000). Docetaxel obtained a 20% response rate as first-line treatment in 37 advanced gastric patients (Sulkes et al, 1994) with a median survival time of 7 months.…”

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.…”