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A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy

  1. Kan Yonemori M.D.1,
  2. Noriyuki Katsumata M.D.1,†,*,
  3. Noboru Yamamoto M.D.1,
  4. Takahiro Kasamatsu M.D.2,
  5. Takuro Yamada M.D.2,
  6. Ryuichiro Tsunematsu M.D.2,
  7. Yasuhiro Fujiwara M.D.1

Article first published online: 26 JUL 2005

DOI: 10.1002/cncr.21287

Issue

Cancer

Cancer

Volume 104, Issue 6, pages 1204–1212, 15 September 2005

Additional Information

How to Cite

Yonemori, K., Katsumata, N., Yamamoto, N., Kasamatsu, T., Yamada, T., Tsunematsu, R. and Fujiwara, Y. (2005), A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy. Cancer, 104: 1204–1212. doi: 10.1002/cncr.21287

Author Information

  1. 1

    Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

  2. 2

    Division of Gynecologic Oncology, National Cancer Center Hospital, Tokyo, Japan

  1. †

    Fax: (011) 81 335423815

*Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

Publication History

  1. Issue published online: 31 AUG 2005
  2. Article first published online: 26 JUL 2005
  3. Manuscript Received: 9 DEC 2005
  4. Manuscript Accepted: 11 MAY 2005
  5. Manuscript Revised: 20 APR 2005

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Keywords:

  • irinotecan;
  • carboplatin;
  • ovarian carcinoma;
  • pharmacokinetics;
  • Chatelut formula

Abstract

BACKGROUND

The objectives of the current study were to determine the maximum tolerated dose (MTD) of irinotecan and carboplatin in combination, to evaluate the efficacy and toxicity of the combination in patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy, and to examine the pharmacokinetics and pharmacodynamics of both drugs by using the Chatelut formula.

METHODS

Patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy were treated with a combination of irinotecan and carboplatin. Carboplatin was administered as a 60-minute intravenous infusion on Day 1 and was followed by irinotecan, which was administered as a 90-minute intravenous infusion on Days 1, 8, and 15. Six dose levels of irinotecan (in mg/m2)/carboplatin (mg · mL/min) were planned: 50 mg/m2/4 mg · mL/minute, 60 mg/m2/4 mg · mL/minute, 50 mg/m2/5 mg · mL/minute, 60 mg/m2/5 mg · mL/minute, 50 mg/m2/6 mg · mL/minute, and 60 mg/m2/6 mg · mL/minute. The carboplatin dosage was calculated by using the Chatelut formula. Treatment was repeated at 28-day intervals.

RESULTS

In total, 19 patients in cohorts of 3 to 5 patients received irinotecan and carboplatin at 5 dose levels. The dose-limiting toxicities were Grade 4 neutropenia and Grade 4 thrombocytopenia. The MTD of the irinotecan/carboplatin combination was 60 mg/m2/5 · mg mL/minute. Partial responses were observed at higher dose levels. Pharmacologic studies demonstrated that administration of the dosage estimated with the Chatelut formula instead of the Chatelut formula with adjustment for serum creatinine resulted in a slightly excessive dose of carboplatin.

CONCLUSIONS

The recommended dose for the Phase II study was irinotecan 60 mg/m2 on Days 1, 8, and 15 with carboplatin 5 mg/mL · minute on Day 1 repeated every 4 weeks. Cancer 2005. © 2005 American Cancer Society.

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