Phase II trial of the use of paclitaxel and gemcitabine as a salvage treatment in metastatic breast cancer.

The purpose of this study was to evaluate gemcitabine plus paclitaxel in heavily pretreated patients with metastatic breast cancer (MBC). Patients with MBC with second or third relapse to anthracycline-containing regimens received a 3-hour infusion of paclitaxel 175 mg/m2 on day 1, and gemcitabine 1.0 g/m2 on days 1, 8, and 15, every 28 days. Because of unacceptable thrombocytopenia seen in the first 5 patients, the gemcitabine schedule was changed to days 1 and 8 (G-1,8) for the remainder of the study, every 21 days. Twenty-nine patients (median age, 46 years; range, 32-68 years) received 137 cycles (median: 4 per patient). The regimen was well tolerated. World Health Organization grades III and IV thrombocytopenia were observed in 5 (18.5%) of the first 27 cycles (G-1,8,15), and in 6 (5.4%) of the 110 subsequent cycles (G-1,8)--p = 0.04 for the difference between schedules. Five patients had grade I and two had grade III neuropathy. Eight patients had grade III neutropenia, two had grade IV neutropenia associated with fever (G-1,8,15), and eight had grades I and II myalgia and fatigue. There were 16 (55%) objective responses (95% CI 36-73%); 5 (17%) complete responses, 11 (38%) partial responses (95% CI 3-30% and 19-56%, respectively), and 6 (20.5%) patients with stable disease. Median response duration was 8 months (range, 4-26 months). Median overall survival was 12 months (range, 4-28+ months), and 1-year and 2-year survival rates were 45% and 30%, respectively. This phase II study demonstrated a manageable toxicity profile with the gemcitabine day 1, 8 schedule in combination with paclitaxel and significant and promising activity in heavily pretreated patients with MBC. A confirmatory phase III trial is warranted.

Gemcitabine and paclitaxel as salvage therapy in metastatic breast cancer.

In a phase II trial, 29 patients with anthracycline-pretreated or anthracycline-resistant metastatic breast cancer in whom anthracycline-containing first- or second-line chemotherapy failed received combination paclitaxel (Taxol)/gemcitabine (Gemzar). The initial regimen of paclitaxel at 175 mg/m2 on day 1 and gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle was given to five patients for a total of 27 cycles. The regimen resulted in excessive thrombocytopenia and was subsequently changed to gemcitabine at the same dose on days 1 and 8 of a 21-day cycle, with study treatment being given for a maximum of eight cycles. This regimen was well tolerated. Further evaluation of this regimen in minimally and heavily pretreated patients with advanced breast cancer is warranted.

Phase II trial of the combination of paclitaxel and 5-fluorouracil in the treatment of advanced gastric cancer: a novel, safe, and effective regimen.

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.