Evaluation of Calvert's Formula for Dosage Adjustment of Carboplatin in Japanese Patients with Hormone Refractory Prostate Cancer

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Author(s)

    • TAKAHASHI Kazushige
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • MOTOHASHI Hideyuki
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • MASUDA Satohiro
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • KATSURA Toshiya
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • SEGAWA Takehiko
    • Department of Urology, Graduate School of Medicine, Kyoto University
    • ITO Noriyuki
    • Department of Urology, Graduate School of Medicine, Kyoto University
    • OGAWA Osamu
    • Department of Urology, Graduate School of Medicine, Kyoto University
    • INUI Ken-ichi
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

Abstract

For hormone refractory prostate carcinoma, a combination therapy of paclitaxel and carboplatin is used to expect life extention. We investigated the pharmacokinetics of carboplatin in Japanese prostate cancer patients (<i>n</i>=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 <i>versus</i> time curve (<i>AUC</i>)=5 mg·min/ml), following the intravenous administration of paclitaxel (175 mg/m<sup>2</sup>). 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 (<i>r</i><sup>2</sup>=0.64, <i>p</i><0.01). The actual <i>AUC</i> 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 <i>AUC</i> compared with that in the carboplatin clearance, and a target <i>AUC</i> of 5 mg·min/ml of carboplatin was comparatively safe for Japanese patients with prostate cancer.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 29(7), 1441-1444, 2006-07-01

    The Pharmaceutical Society of Japan

References:  31

Codes

  • NII Article ID (NAID)
    110005602318
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09186158
  • NDL Article ID
    7960582
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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