Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer

Eriko Sato, Ikuko Yano, Mari Jiko, Kazushige Takahashi, Hideyuki Motohashi, Satohiro Masuda, Toshiya Katsura, Hiroyuki Nishiyama, Takehiko Segawa, Noriyuki Ito, Toshiyuki Kamoto, Osamu Ogawa, Ken Ichi Inui

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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 (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/m2). 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 (r2=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.

Original languageEnglish
Pages (from-to)1441-1444
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume29
Issue number7
DOIs
Publication statusPublished - Jul 12 2006
Externally publishedYes

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Carboplatin
Prostatic Neoplasms
Hormones
Area Under Curve
Paclitaxel
Creatinine
Pharmacokinetics
National Cancer Institute (U.S.)
Leukopenia
Platinum
Intravenous Infusions
Thrombocytopenia
Intravenous Administration
Prostate

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer. / Sato, Eriko; Yano, Ikuko; Jiko, Mari; Takahashi, Kazushige; Motohashi, Hideyuki; Masuda, Satohiro; Katsura, Toshiya; Nishiyama, Hiroyuki; Segawa, Takehiko; Ito, Noriyuki; Kamoto, Toshiyuki; Ogawa, Osamu; Inui, Ken Ichi.

In: Biological and Pharmaceutical Bulletin, Vol. 29, No. 7, 12.07.2006, p. 1441-1444.

Research output: Contribution to journalArticle

Sato, E, Yano, I, Jiko, M, Takahashi, K, Motohashi, H, Masuda, S, Katsura, T, Nishiyama, H, Segawa, T, Ito, N, Kamoto, T, Ogawa, O & Inui, KI 2006, 'Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer', Biological and Pharmaceutical Bulletin, vol. 29, no. 7, pp. 1441-1444. https://doi.org/10.1248/bpb.29.1441
Sato, Eriko ; Yano, Ikuko ; Jiko, Mari ; Takahashi, Kazushige ; Motohashi, Hideyuki ; Masuda, Satohiro ; Katsura, Toshiya ; Nishiyama, Hiroyuki ; Segawa, Takehiko ; Ito, Noriyuki ; Kamoto, Toshiyuki ; Ogawa, Osamu ; Inui, Ken Ichi. / Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer. In: Biological and Pharmaceutical Bulletin. 2006 ; Vol. 29, No. 7. pp. 1441-1444.
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AU - Sato, Eriko

AU - Yano, Ikuko

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AU - Takahashi, Kazushige

AU - Motohashi, Hideyuki

AU - Masuda, Satohiro

AU - Katsura, Toshiya

AU - Nishiyama, Hiroyuki

AU - Segawa, Takehiko

AU - Ito, Noriyuki

AU - Kamoto, Toshiyuki

AU - Ogawa, Osamu

AU - Inui, Ken Ichi

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N2 - 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 (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/m2). 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 (r2=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.

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