Pharmacogenetic analysis of paclitaxel in breast cancer

3058 Background: Paclitaxel is one of the most active single agents in the treatment of breast cancer and is an important component of many commonly used combination regimens. Despite its clinical activity, variability in toxicity and response remain a major problem for patients receiving paclitaxel. Significant variability (4–10 fold) in paclitaxel clearance may contribute to the unpredictability of clinical outcomes. Methods: To determine the contribution of inherited differences in drug metabolism and excretion to the pharmacokinetics and progression-free survival in patients receiving paclitaxel, genomic DNA was isolated from the plasma of 93 patients with high-risk primary (84% stage II with ≥ 10 axillary nodes, stage IIIA or stage IIIB inflammatory carcinoma) or stage IV (16%) breast cancer. Patients received paclitaxel 575–775 mg/m2 infused over 24 hours, doxorubicin 165 mg/m2 as a continuous infusion over 96 hours, and cyclophosphamide 100 mg/kg. Median overall follow-up was 52 months. Ten polymor...