Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer

To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel.

Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity.

Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients.

1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated.