title: Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy.
abstract: 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.
  
  
  
  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/m (level 2) and then 80 mg/m (level 3), whereas the dosage of irinotecan remained the same (150 mg/m). The primary end point for the escalation study was acute DLT that occurred within 2 cycles of chemotherapy.
  
  
  
  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.
  
  
  
  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/m, respectively.
authors.affiliation: *Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita; †Department of Obstetrics and Gynecology, Kaizuka Municipal Hospital, Kaizuka; and ‡Department of Obstetrics and Gynecology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.forename: Eriko
authors.initials: E
authors.lastname: Yokoi
authors.forename: Takao
authors.initials: T
authors.lastname: Owa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kozasa
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamashita
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoki
authors.forename: Tateki
authors.initials: T
authors.lastname: Tsutui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010094:Oxonic Acid / Q000627:therapeutic use*; D005641:Tegafur / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin