Paclitaxel and weekly 24-hour infusion of 5-fluorouracil/folinic acid in advanced gastric cancer.

The current phase II study evaluates the safety and efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and 5-fluorouracil (5-FU) plus folinic acid in patients with advanced gastric cancer. Paclitaxel 175 mg/m2 was given intravenously over 3 hours on days 1 and 22; folinic acid 500 mg/m2 given intravenously over 2 hours followed by 5-FU 2,000 mg/m2 given intravenously over 24 hours was administered on days 1, 8, 15, 22, 29, and 36. Six weeks of treatment were considered one cycle, and each cycle was followed by 2 weeks off treatment. Twenty-two patients (six women and 16 men) with advanced/metastatic gastric cancer were entered on trial. All patients are evaluable for response and toxicity. None had received prior chemotherapy. Radiologically metastatic sites included gastric lymph nodes (64%), liver (36%), lungs (18%), peritoneum (18%), bone (9%), and skin (5%). No complete responses were observed. Seven patients (32%; 95% confidence interval, 12% to 52%) had a partial response. Sites of partial responses included the lungs, skin, lymph nodes, and locally advanced tumor. Twelve patients (55%) had stable disease and three (14%) had disease progression. At a median follow-up of 12 months (range, 1 to 17+ months), the median overall survival for all patients was 11 months (range, 1 to 17+ months; 95% confidence interval, 6.8 to 18.2) and the median progression-free interval was 8 months (range, 1 to 13+ months; 95% confidence interval, 4.7 to 9.8). Severe nonhematologic toxicities were alopecia (45%), fever/infection (9%), diarrhea (5%), and nausea/vomiting (5%). Grade 3/4 neutropenia occurred in three patients (14%). In summary, paclitaxel given every 3 weeks in combination with once-weekly, 24-hour continuous infusions of 5-FU/folinic acid is active in advanced gastric cancer and appears to achieve response rates comparable to regimens like etoposide/folinic acid/5-FU or 5-FU/doxorubicin/methotrexate. The toxicity of this new combination is moderate and allows treatment in an outpatient setting. Ongoing studies are evaluating the activity of paclitaxel combined with weekly continuous infusions of 5-FU/folinic acid with or without cisplatin.