RT Journal Article
SR Electronic
T1 Phase II Trial of Irinotecan and Raltitrexed in Chemotherapy-naive Advanced Colorectal Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1391
OP 1396
VO 25
IS 2B
A1 SILVANA CHIARA
A1 MARIA TERESA NOBILE
A1 LAURA TOMASELLO
A1 MIRKO ACQUATI
A1 PAOLA TAVEGGIA
A1 CARMELINA MUROLO
A1 PIERLUIGI PERCIVALE
A1 RICCARDO ROSSO
YR 2005
UL http://ar.iiarjournals.org/content/25/2B/1391.abstract
AB Background: Irinotecan and raltitrexed are active agents in advanced colorectal cancer (ACC) and preclinical data suggest a remarkable synergistic activity. Phase I studies demonstrated that single-agent full dose of both drugs can be administered with moderate toxicity. The aim of this phase II trial was to assess the activity and tolerability of the combination in untreated ACC. Patients and Methods: Forty-eight patients entered the trial and received irinotecan 350 mg/m2 d.1 and raltitrexed 3 mg/m2 d.2, every three weeks. After recruitment of the first 16 patients, grade III-IV toxicity was observed in 6 patients (38%). Therefore, an amendment reduced by 15% the dose of both drugs (irinotecan 300 mg/m2, raltitrexed 2.6 mg/m2). Results: A total of 290 cycles were administered (range 1-18, median number 6). According to intention-to-treat analysis, the overall response rate was 27% (95% confidence interval 16%-42%), including 3 complete responses and 10 partial responses. The median duration of response was 10 months, while median progression-free survival and overall survival were 5 and 14 months, respectively. In the first 16 patients, the main toxicities were grade III-IV diarrhea in 25% and grade III-IV neutropenia in 13%. In the subsequent 32 patients, they were grade III-IV diarrhea in 34% and grade III neutropenia in 6%. Two toxic deaths occurred. Conclusion: The combination irinotecan-raltitrexed is an active regimen, but the significant incidence of side-effects requires accurate patient selection and, eventually, new schedules. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved