Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.
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.
Sato
Eriko
E
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
Yano
Ikuko
I
Jiko
Mari
M
Takahashi
Kazushige
K
Motohashi
Hideyuki
H
Masuda
Satohiro
S
Katsura
Toshiya
T
Nishiyama
Hiroyuki
H
Segawa
Takehiko
T
Ito
Noriyuki
N
Kamoto
Toshiyuki
T
Ogawa
Osamu
O
Inui
Ken-ichi
K
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*
D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin; D017239:Paclitaxel