Doxorubicin and paclitaxel in advanced breast carcinoma - Importance of prior adjuvant anthracycline therapy

BACKGROUND. The authors undertook a Phase II multicenter trial to assess th e efficacy and toxicity of doxorubicin and paclitaxel in combination in the treatment of patients with metastatic breast carcinoma. METHODS. Doxorubicin (50 mg/m(2), bolus) followed by paclitaxel (175 mg/m(2 ) over 3 hours) was administered every 21 days (for a maximum of 10 cycles) as first-line chemotherapy in 77 patients, 41 of whom had received prior a djuvant chemotherapy. Monitoring of cardiac function (left ventricular ejec tion fraction[LVEF]) and total doxorubicin cumulative dose were included in the study protocol. RESULTS. Grade 4 hematologic toxicities were neutropenia (58%) and thromboc ytopenia (4%). Neutropenic fever occurred in 9% of patients. Nonhematologic Grade 4 toxicity was Limited to mucositis (3%). Grade 3 toxicities were ne utropenia (35%), anemia (3%), alopecia (93%), peripheral neuropathy (18%), arthralgia/myalgia (8%), and mucositis (9%). No clinical cardiotoxicity (Gr ades 3 or 4) occurred. Treatment was discontinued in 5 patients who showed a decrease of LVEF of greater than 15% during therapy. Of 73 patients asses sable for response, 15 were complete response, 42 partial response, 15 stab le disease, and 1 disease progression; overall response rate being 78% (95% confidence interval [CI], 67-87). Median follow-up was 22 months. Median t ime to progression (TP) was 10 months (95% CI, 7-12). Time to progression w as poorer in cases with adjuvant anthracycline therapy than those without a djuvant chemotherapy (7 vs. 12.3 months; P = 0.022), but TP in patients wit h adjuvant chemotherapy not containing anthracyclines was not different fro m the cases without adjuvant chemotherapy (8.6 months). Estimated 2-year su rvival was 51% (standard error, 7%). CONCLUSIONS. Our results confirm that the combination of paclitaxel and dox orubicin is effective in the treatment of metastatic breast carcinoma, and that it is well tolerated. No clinical cardiotoxicity was observed on close cardiac monitoring, and prior adjuvant anthracycline treatment compromised its efficacy. Cancer 2000;89:2169-75. (C) 2000 American Cancer Society.