Dose-Dense Weekly Docetaxel in Metastatic Breast Cancer

Weekly administration of taxanes as palliative treatment in metastatic breast cancer has been reported with significantly reduced hematologic toxicity and comparable efficacy to standard every-3-week protocols. This study update provides mature results with weekly docetaxel (Taxotere) in a larger patient population.

Eligibility criteria for this study included measurable disease, prior chemotherapy for metastatic disease, and ECOG (Eastern Cooperative Oncology Group) performance status £ 2.

The protocol design consisted of docetaxel, 40 mg/m²/30 min infusion weekly ´ 6, followed by a 2-week rest. Patients were premedicated with dexamethasone, 8 mg intravenously before docetaxel administration, followed by oral dexamethasone, 4 mg on the next day.

The patient characteristics were as follows: 41 evaluable patients; ECOG performance status 0/1/2: 21/18/2 patients; median age: 55.2 years (range: 47–71 years); all had one to three previous chemotherapy protocols; prior epirubicin (Ellence): 25 (61%); prior paclitaxel (Taxol): 6 (15%); delivered median dose intensity of docetaxel: 36 mg/m²/week.

Toxicity included leukopenia (grade 2/3/4): 27%/10%/2% (maximum tolerated dose, 45 mg/m²/week); no febrile neutropenia; nail toxicity (1/2): 34%; edema (1): 8%; no grade 2–4 cumulative sensory neuropathy; alopecia (2/3): 76%; asthenia (1/2): 17%; conjunctivitis (2): 2%; delay of treatment by 1 week: 7%; dose reduction to 35 mg/m²/week: 10%.

Response rates were as follows: complete response: 12%; partial response: 36%; no change: 40%; progressive disease: 12%; 3 of 6 patients with prior weekly paclitaxel responded to weekly docetaxel. Median duration of remission was 8.8 months (range: 2–12 months); median survival time was 12.8 months.

CONCLUSION: Weekly docetaxel has definite activity in chemotherapy-pretreated breast cancer that is comparable to 100 mg/m² every 3 weeks, but with substantially reduced grade 3/4 leukocyte toxicity. The low incidence of leukopenia facilitates combination therapy without compromise of docetaxel dosing. The recommended weekly dose is 40 mg/m², as further dose escalation results in grade 3/4 cumulative leukopenia, indicating a narrow toxicity margin and a maximum tolerated dose between 40 and 45 mg/m².