Excessive Neutropenia for Weekly Everolimus + Docetaxel
Dose-limiting neutropenia, variable drug clearance for patients with metastatic breast cancer
FRIDAY, April 27 (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, M.D., 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 75 mg/m² intravenously on day one of a 21-day cycle) and everolimus (20 to 50 mg orally on days one and eight of a 21-day cycle) to determine the maximum tolerated dose.
The researchers found that the first two 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 40 mg/m², day eight 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.
"Weekly everolimus in combination with docetaxel every three 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.