(HealthDay News) – For patients with metastatic breast cancer, weekly treatment with everolimus plus docetaxel every three weeks results in dose-limiting neutropenia and variable clearance of both drugs, according to a Phase 1 study published in the May 1 issue of Cancer.

Stacy Moulder, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues conducted a Phase 1 trial involving 15 patients with metastatic breast cancer who were treated with docetaxel (40 to 75mg/m² intravenously on day 1 of a 21-day cycle) and everolimus (20 to 50mg orally on days 1 and 8 of a 21-day cycle) to determine the maximum tolerated dose.

The researchers found that the first 2 patients developed dose-limiting toxicity, prompting a dose reduction. Among the treated patients, dose-limiting toxicities included grade 3 mucositis in one patient, prolonged grade 4 neutropenia in one patient, and grade 3 infection/febrile neutropenia in three patients. Despite a reduction in docetaxel dose to 40mg/m², day 8 of everolimus was typically held due to neutropenia. Pharmacokinetic analyses demonstrated highly variable clearance of both docetaxel and everolimus. The study was ended due to lack of efficacy and toxicity concerns.

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“Weekly everolimus in combination with docetaxel every 3 weeks was associated with excessive neutropenia and variable clearance of both drugs, making combination therapy unpredictable, even at low doses of both drugs,” the authors write.

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