The M. D. Anderson Cancer Center experience with Taxol in metastatic breast cancer

Taxol was evaluated in metastatic breast cancer in three trials. In the first, a phase II study, 25 patients who had received only one prior regimen of chemotherapy received Taxol (starting dose of 250 mg/m2). The response rates were 12% complete, 44% partial, and 32% minor. The median duration of response was 9 months (range, 3 to 19 months). The median survival was 20 months (range, 5 to 29+ months). Toxic effects were granulocytopenia less than 500/mm3 in 85% of all courses but serious infection in only 6% of courses, myalgias, and cumulative neuropathy. The second trial was a phase I study of Taxol by 24-hour infusion sequenced with doxorubicin by 48-hour infusion as initial chemotherapy for metastatic disease. In arm 1, Taxol preceded doxorubicin. The starting doses were 125 mg/m2 Taxol, 60 mg/m2 doxorubicin. Neupogen (5 micrograms/kg) was given subcutaneously on days 5 through 19. Ten patients received 96 courses. The maximum tolerated dose was defined by mucositis and infection at the starting dose. Cumulative thrombocytopenia occurred in subsequent courses. The unexpectedly severe toxic effects at doses that were low by comparison to other studies suggested schedule-related toxicity. Therefore, in arm 2 the sequence has been reversed: doxorubicin precedes Taxol. Doses have been escalated to 180 mg/m2 Taxol with 60 mg/m2 doxorubicin without dose-limiting toxic effects occurring. The third trial, a phase II study in patients who have received three or more prior chemotherapy regimens, is ongoing. Twenty-one of a planned 35 patients have been entered. Taxol has shown significant antitumor activity in minimally pretreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)