Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol Investigational Trials Group, Australia and New Zealand

When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment