title: Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.
abstract: For hormone refractory prostate carcinoma, a combination therapy of paclitaxel and carboplatin is used to expect life extension. We investigated the pharmacokinetics of carboplatin in Japanese prostate cancer patients (n=10, 55-72 years), and evaluated the usefulness of Calvert's formula in the individualized dosing adjustment. They were intravenously administered carboplatin (area under the free plasma concentration versus time curve (AUC)=5 mg.min/ml), following the intravenous administration of paclitaxel (175 mg/m(2)). The dosage of carboplatin for each patient was determined with Calvert's formula using individual creatinine clearance values. Plasma concentration of total platinum was measured sequentially and the pharmacokinetic parameters of carboplatin were determined in each patient. Plasma concentration of total carboplatin after intravenous infusion well fitted the two-compartment model. Carboplatin clearance was 62.0+/-12.7 ml/min (mean+/-S.D.), and linearly related to the individual creatinine clearance (r(2)=0.64, p<0.01). The actual AUC for total carboplatin was 8.20+/-1.11 mg.min/ml, and its inter-individual variability was decreased to 65% of that in carboplatin clearance, indicating the effectiveness of Calvert's formula for dosage adjustment of carboplatin. Leucopenia of grade 4 according to the National Cancer Institute's Common Toxicity Criteria was found in one patient, but no patient demonstrated thrombocytopenia. In conclusion, determining carboplatin dosage based on Calvert's formula decreased the inter-individual variability in the actual AUC compared with that in the carboplatin clearance, and a target AUC of 5 mg.min/ml of carboplatin was comparatively safe for Japanese patients with prostate cancer.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Sato
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yano
authors.forename: Mari
authors.initials: M
authors.lastname: Jiko
authors.forename: Kazushige
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Motohashi
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Toshiya
authors.initials: T
authors.lastname: Katsura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Takehiko
authors.initials: T
authors.lastname: Segawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008962:Models, Theoretical; D017239:Paclitaxel / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin; D017239:Paclitaxel