Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy.

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/m 2 (level 2) and then 80 mg/m 2 (level 3), whereas the dosage of irinotecan remained the same (150 mg/m 2 ). 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/m 2 , respectively.