Prospective evaluation of body surface area as a determinant of paclitaxel pharmacokinetics and pharmacodynamics in women with solid tumors: Cancer and leukemia group B study 9763

Purpose: To study a fixed dose (360 mg) of paclitaxel given i.v. over 3 hours to female patients, and to evaluate prospectively the relationships between the following: body surface area and toxicity; body surface area and pharmacokinetics; and pharmacokinetics and toxicity. Experimental Design: The eligibility criteria included the following: female sex; solid tumors; no more than one prior chemotherapy regimen; no prior paclitaxel; performance status of 0 to 2; and normal organ function. Paclitaxel plasma concentrations were quantified by high-performance liquid chromatography. The area under the curve, total body clearance, and hours,above 0.05 mumol/L (T > 0.05) were calculated. Results: Thirty-two patients were enrolled, and 29 patients received the correct dose and regimen. For statistical analyses, 26 patients had complete follow-up blood counts, 23 patients had complete data to correlate blood counts and area under the curve, and 25 patients had data to correlate blood counts and T > 0.05. The main toxicity was neutropenia of grade 3 and 4 severity in 21% and 25% of patients, respectively, in cycle 1. The worst grade of any toxicity, nadir WBC and absolute neutrophil count, and survival fractions were assessed; no significant relationship was found between body surface area and any measure of toxicity. Body surface area correlated inversely with area under the curve (r = -0.67; P < 0.001) and correlated with total body clearance (r = 0.69; P < 0.001), but body surface area did not correlate with T > 0.05. Neither area under the curve nor total body clearance were correlated with nadir absolute neutrophil count or survival fractions, but a significant correlation was found between T > 0.05 and log(nadir absolute neutrophil count; r = -0.41; P = 0.04). Conclusions: These results suggest that fixed dosing of paclitaxel is feasible in women, which would simplify the administration of this drug.