Phase I study of Taxol, doxorubicin, plus granulocyte-colony stimulating factor in patients with metastatic breast cancer.

The objective of this phase I trial was to determine the maximal tolerated dose (MTD) of Taxol and doxorubicin administered as a simultaneous intravenous infusion over 72 hours every 21 days. Granulocyte-colony stimulating factor (G-CSF) 10 micrograms/kg, was administered on days 4-18 of each cycle. The treated population consisted of metastatic breast cancer patients previously untreated with chemotherapy for metastatic disease, who had not received doxorubicin in the adjuvant setting and who had bidimensionally measurable disease. The MTD was determined to be 75 mg/m2 of doxorubicin and 160 mg/m2 of Taxol. The dose-limiting toxicity of the combination was clinical typhlitis in three of three patients. Other significant toxicities included grade 3 diarrhea at the higher dose levels and grade 4 neutropenia in all patients. Eighteen patients were treated on this initial phase I study. The overall response rate was 62%, with 6% complete responses and 56% partial responses. The combination of doxorubicin and Taxol by 72-hour continuous infusion with G-CSF is an active regimen in patients with metastatic breast cancer.