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.
OBJECTIVE
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.


METHODS
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 micromol/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.
Miller
Antonius A
AA
Wake Forest University, Winston-Salem, North Carolina 27157, USA. aamiller@wfubmc.edu
Rosner
Gary L
GL
Egorin
Merrill J
MJ
Hollis
Donna
D
Lichtman
Stuart M
SM
Ratain
Mark J
MJ
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001830:Body Surface Area; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel