Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies

Muneaki Shimada, Hiroyuki Fujiwara, Shinya Sato, Tetsuro Oishi, Hiroaki Itamochi, Shizuo Machida, Yuji Takei, Tasuku Harada, Mitsuaki Suzuki, Junzo Kigawa

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Purpose: Although the pharmacokinetic mechanism of nedaplatin (NDP) is similar to carboplatin, the dose of NDP is typically determined by body surface area and not by the area under the curve (AUC). We conducted a phase I study to determine the AUC-calculated optimal dosage of NDP used in combination chemotherapy with irinotecan (CPT-11) for gynecologic malignancies. Methods: A total of 15 patients who were to undergo combination chemotherapy consisting of NDP and CPT-11 were enrolled in this study. The dose of CPT-11 was administered at a fixed dose of 60 mg/m 2 and that of NDP was gradually increased from 8 to 12 μg h/mL (AUC). The individual dose of NDP was calculated based on cratinine clearance of the patient according following formula: Dose NDP = AUC × CL NDP, where CL NDP = 0.0738 × creatinine clearance + 4.47 (Ishibashi's formula). Results: One patient had dose-limiting toxicity (DLT) at level 1, and two patients suffered DLT at level 3. The dosage of NDP at AUC 12 was determined to be the maximum tolerated dose in combination chemotherapy with CPT-11, even though only two of the six patients showed DLT at level 3. Conclusions: The recommended dosage of NDP calculated by AUC with Ishibashi's fomula was set to AUC 10 in combination chemotherapy with CPT-11.

Original languageEnglish
Pages (from-to)33-38
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume70
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1
Externally publishedYes

Keywords

  • AUC
  • CPT-11
  • Chemotherapy
  • Nedaplatin
  • Phase I study

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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