Improvement of safety profile of docetaxel by weekly administration in patients with metastatic breast cancer.

Background: This is a retrospective cohort study on the safety and efficacy profiles of weekly docetaxel at varying doses in patients with pretreated metastatic breast cancer.
Patients and Methods: Twenty-five anthracycline-pretreated patients received docetaxel administered on a weekly basis, as a one-hour infusion, at various dosage levels (25, 30, 35, 40 mg/m2) depending on their baseline Karnofsky index. Each 8-week cycle consisted of 6 weeks of drug infusion, followed by a 2-week rest period.
Results: Of the 25 patients investigated, none achieved complete response (CR), while 9 patients showed partial response (PR), which corresponds to an overall response rate of 36%. Five patients (20%) maintained stable disease (SD), whereas 11 patients (44%) suffered tumor progression (PD) during treatment. Clinical response (defined as PR+SD) was achieved in 14 patients (56%). Median time to progression was 231 days (95% CI, 187-275). The baseline Karnofsky index was 87% +/- 9% (range: 70-100). Patients pretreated with anthracyclines only tended to have a better response than anthracycline/paclitaxel-pretreated patients (n = 6, p = 0.054). Higher dosages were associated with neurotoxicity, skin/nail toxicity, leukopenia, nausea/vomiting, fatigue/asthenia, peripheral edema, but not with diarrhea and alopecia. The cumulative dose per patient was largest for a weekly docetaxel dosage of 35 mg/m2 and almost as large for 30 mg/m2.
Conclusion: Balancing toxicity vs. efficacy/cumulative dosage delivered, our results support weekly administration of docetaxel at dosages of 30-35 mg/m2 in metastatic breast cancer. Response in patients pretreated with anthracyclines and taxanes may be poorer than in those pretreated with anthracyclines only.