Bi-weekly docetaxel in the adjuvant treatment of node-positive or high-risk breast cancer patients: phase I study of the Shiga Breast Cancer Study Group.

Background: A phase I study of bi-weekly docetaxel was performed to determine the maximum tolerated dose (MTD) as well as the incidence and severity of toxicities in patients with high-risk node-negative and node-positive breast cancer.

Methods: Docetaxel was administered every 14 days to postoperative breast cancer patients who were axillary lymph node-positive or considered at high-risk. After the completion of six cycles of docetaxel, all patients received epirubicin + cyclophosphamide every 21 days for four cycles. The docetaxel dose was escalated in a stepwise fashion as follows: 45, 50, 55, 60, 65, and 70 mg/m(2) in levels 1, 2, 3, 4, 5, and 6, respectively. Patients were treated in cohorts of three to six per group using a standard phase I study design. The MTD was considered the dose level at which three of three patients or more than three of six patients experienced dose-limiting toxicity (DLT) in the first cycle.

Results: Twenty patients were enrolled and received a total of 110 cycles of chemotherapy. The MTD was not reached until level 5. Since three DLTs (grade 3 diarrhea, n = 2; grade 3 constipation, n = 1), were observed in five patients at level 6, level 6 was judged as the MTD. The recommended dose of bi-weekly docetaxel for a phase II trial is 65 mg/m(2).

Conclusions: The MTD of bi-weekly docetaxel was 70 mg/m(2). Further evaluation is warranted to confirm the safety and efficacy in the treatment of early-stage breast cancer.