Paclitaxel combinations as front-line and salvage chemotherapy regimens in advanced breast cancer.

Thirty-two patients with advanced breast cancer have been treated with epirubicin 90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six courses have been administered; dose-related grade 4 neutropenia was observed in 66\% of the courses, with 12 episodes of febrile neutropenia. Two patients showed a decline of left ventricular ejection fraction below 50\% after six courses, but no signs of congestive heart failure have been reported. The response rate is 76\% (95\% confidence interval, 56\% to 90\%), with 14\% complete remissions. This level of activity is encouraging considering that 84\% of the patients had failed adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive disease following hormone therapy for metastasis. In another study, the toxicity and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated; vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20 patients), and the courses were repeated every 3 weeks. Thirty-four previously treated patients with advanced breast cancer entered the study; 20 had received one prior line of chemotherapy, II had two lines, and three patients had three lines. Thirty-two patients had been exposed to anthracyclines. Grade 4 neutropenia was observed in 64\% of the courses, with 13 episodes of febrile neutropenia; four episodes of grade 3 mucositis have been reported with vinorelbine days 1 and 3. A delay in the administration of chemotherapy was necessary in 17\% of the courses with vinorelbine days 1 and 8 and 16\% of the courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced or the drug omitted on day 8 in 86\% of the courses and on day 3 in 16\% of the course. An objective response was achieved in 43\% of the patients. In conclusion, the combination of paclitaxel plus vinorelbine is an active salvage regimen and can be administered at greater dose intensity with the day 1 and 3 schedule.