Background: The authors undertook a Phase II multicenter trial to assess the efficacy and toxicity of doxorubicin and paclitaxel in combination in the treatment of patients with metastatic breast carcinoma.
Methods: Doxorubicin (50 mg/m2, bolus) followed by paclitaxel (175 mg/m2 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 adjuvant chemotherapy. Monitoring of cardiac function (left ventricular ejection fraction[LVEF]) and total doxorubicin cumulative dose were included in the study protocol.
Results: Grade 4 hematologic toxicities were neutropenia (58%) and thrombocytopenia (4%). Neutropenic fever occurred in 9% of patients. Nonhematologic Grade 4 toxicity was limited to mucositis (3%). Grade 3 toxicities were neutropenia (35%), anemia (3%), alopecia (93%), peripheral neuropathy (18%), arthralgia/myalgia (8%), and mucositis (9%). No clinical cardiotoxicity (Grades 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 assessable for response, 15 were complete response, 42 partial response, 15 stable disease, and 1 disease progression; overall response rate being 78% (95% confidence interval [CI], 67-87). Median follow-up was 22 months. Median time to progression (TP) was 10 months (95% CI, 7-12). Time to progression was poorer in cases with adjuvant anthracycline therapy than those without adjuvant chemotherapy (7 vs. 12.3 months; P = 0.022), but TP in patients with adjuvant chemotherapy not containing anthracyclines was not different from the cases without adjuvant chemotherapy (8.6 months). Estimated 2-year survival was 51% (standard error, 7%).
Conclusions: Our results confirm that the combination of paclitaxel and doxorubicin 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.