PACLITAXEL IN METASTATIC BREAST-CANCER - A TRIAL OF 2 DOSES BY A 3-HOUR INFUSION IN PATIENTS WITH DISEASE RECURRENCE AFTER PRIOR THERAPY WITH ANTHRACYCLINES

Background: To date, anthracyclines are the most active drugs against breast tumors, and the taxane paclitaxel (Taxol) looks very promising, Both classes of drugs are affected by cellular multidrug-resistance m echanisms, and therefore their sequential use raises the possibility o f clinical cross-resistance. It is therefore important to assess the a ctivity of paclitaxel in patients with clinical resistance to anthracy clines. Purpose: We assessed the safety and efficacy of paclitaxel adm inistered by the logistically convenient 3-hour infusion to breast can cer patients who had disease progression within 12 months since prior therapy with anthracyclines, Methods: Fifty-one patients with metastat ic breast cancer who had all relapsed or whose disease had progressed within 12 months from completion of an anthracycline-containing chemot herapy protocol (six receiving adjuvant therapy, 19 receiving neoadjuv ant therapy, and 26 receiving treatment for metastatic disease) were e nrolled in this phase II trial from June 1992 to May 1994. After medic ation to prevent type I acute hypersensitivity reactions, paclitaxel w as given intravenously over 3 hours at 175 mg/m(2) to the first 15 pat ients and at 225 mg/m(2) to the next 36 patients. The median age was 5 0 years (range, 31-62 years), and the median Eastern Cooperative Oncol ogy Group performance status was 0 (range, 0-2). Results: Patients rec eived a median of five cycles (range, one to 11 cycles). After initial doses of 175 and 225 mg/m(2), paclitaxel could be increased by 25 mg/ m(2) in 73% and 58% of cycles, respectively. Among 50 assessable patie nts, seven achieved a complete response and 12 achieved a partial resp onse (response rate, 38% [95% confidence interval = 25%-53%]). The med ian duration sponse was 7 months (range, months), and the median time to disease progression for all patients was 5 months. Grade 4 neutrope nia occurred in 3% of the cycles and in 12% of the patients and was ne ver associated with fever and infection. Common toxic effects were mya lgia and arthralgia (94% of the patients; 4% grade 3), peripheral neur opathy (92% of the patients; 8% grade 3), and alopecia (all patients). Pruritus and neuropathy were significantly more frequent and severe, respectively, with the higher dose (P<.01 by chi(2) test). Frequency a nd severity of other toxic effects were similar at either starting dos e. Ten patients had symptoms of neuro-optic toxicity. Only one patient had a grade 2 hypersensitivity reaction. Conclusions: Paclitaxel at s tarting doses of 175 and 225 mg/m(2) given as a 3-hour infusion can sa fely be administered to, and is active in women whose disease has prog ressed after prior treatment with anthracyclines. There was evidence o f increased toxicity at the higher dose but no suggestion of better ef ficacy. Implication: Paclitaxel by a 3-hour infusion in combination wi th doxorubicin should be investigated in patients with metastatic brea st cancer. Unless randomized trials demonstrate greater efficacy of th e more toxic higher dose, it is suggested that a dose of 175-200 mg/m( 2) be administered with the 3-hour infusion schedule.