Objective: We conducted a phase I-II study to determine the maximum tolerated dose (MTD), toxicity and activity of weekly docetaxel administration in pretreated metastatic breast cancer patients. Methods: In phase I, cohorts of 3women with pretreated metastatic breast cancer were treated with a 1-hour infusion of docetaxelat 30, 35, 40 mg/m2/week after premedication with two doses of dexamethazone 8 mg 12 h apart. Subsequently, a cohort of 28 women was treated at the MTD for 24 consecutive weeks in a phase II setting and was assessed for toxicity and activity. Results: Three patients were treated at each of the first two dose levels; 9 patients were treated at the 3rd level (40 mg/m2/week). Dose-limiting toxicities (DLTs) were experienced at that level by 2/6 patients of the first two accrued groups and in 2/3 patients of the 3rd (confirmation) group, thus establishing the subsequent phase II dose at 35 mg/m2/week. Two out of 28 evaluable patients (7.1%, 95% CI 0–16.7) showed complete responses, whereas 8 (28.6%, 95% CI 11.8–45.3) showed partialresponses, and an objective response rateof 35.7% (95% confidence interval, CI 18–53.5%). In addition, 8 patients (28.6%) had stable disease. The median time to progression and overall survival were 5 (range 1–15) and 15months (95% CI 7–23), respectively. One patient experienced 1 episode of grade 3 neutropenia. Severe asthenia was the main reason for interruption of chemotherapy (10 patients, 35.5%). Conclusions: In pretreated metastatic breast cancer patients, the sustained weekly administration of docetaxel, even though it demonstrated an activity similar to a 3-weekly schedule could not be maintained for the planned 24 weeks due to the progressive emergence of nonhematological side effects that approached DLTs.

Keywords:
Metastatic breast cancer, Docetaxel
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2005
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