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Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy
  1. Seiji Mabuchi, MD, PhD*,
  2. Eriko Yokoi, MD*,
  3. Takao Owa, MD*,
  4. Katsumi Kozasa, MD*,
  5. Michiko Yamashita, MD*,
  6. Eiji Kobayashi, MD*,
  7. Takuji Tomimatsu, MD, PhD*,
  8. Takeshi Yoki, MD, PhD,
  9. Tateki Tsutui, MD, PhD and
  10. Tadashi Kimura, MD, PhD*
  1. *Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita;
  2. Department of Obstetrics and Gynecology, Kaizuka Municipal Hospital, Kaizuka; and
  3. Department of Obstetrics and Gynecology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan.
  1. Address correspondence and reprint requests to Seiji Mabuchi, MD, PhD, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail:


Objectives This study aimed to determine the maximum tolerated dose and acute dose-limiting toxicities (DLTs) of intravenous irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.

Methods Irinotecan was administered intravenously over the course of 90 minutes on day 1, and S-1 was given orally in 2 divided doses from days 1 to 14 of a 21-day cycle. The dose of S-1 was escalated in a stepwise fashion from 40 (level 1) to 60 mg/m2 (level 2) and then 80 mg/m2 (level 3), whereas the dosage of irinotecan remained the same (150 mg/m2). The primary end point for the escalation study was acute DLT that occurred within 2 cycles of chemotherapy.

Results Twelve patients were enrolled and treated over 3 dose levels. Their median age was 47 years (range, 28–48 years). At level 1, one episode of grade 3 anemia and a grade 3 fatigue were observed, but no DLT developed. At level 2, the first patient experienced febrile neutropenia, which was considered to be a DLT. To evaluate the toxicity of this dose level, 5 more patients were evaluated. However, no DLT developed in these patients. At level 3, although grade 1 to 2 hematological and nonhematological toxicities developed, no DLT occurred.

Conclusions In women with advanced or recurrent cervical cancer previously treated with platinum-based chemotherapy, S-1 plus irinotecan in a triweekly setting is a reasonable treatment regimen with an acceptable toxicity profile. The recommended doses of S-1 and irinotecan for this regimen are 80 and 150 mg/m2, respectively.

  • Cervicaxl cancer
  • Chemotherapy
  • S-1
  • Irinotecan
  • Non-platinum doublet
  • Phase I study

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  • The authors declare no conflicts of interest.

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