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Irinotecan in the Treatment of Advanced Colorectal Cancer in Patients Pretreated With Fluorouracil-Based Chemotherapy

A Study to Determine Recommendable Therapeutic Dosage

Viéitez, Jose M., M.D., Ph.D.; Carrasco, Juan, M.D.; Esteban, Emilio, M.D., Ph.D.; Fra, Joaquín, M.D.; Alvarez, Elena, M.D.; Muñiz, Isabel, M.D.; Sala, Marian, M.D.; Buesa, Jose M., M.D., Ph.D.; Lacave, Angel Jiménez, M.D., Ph.D.

American Journal of Clinical Oncology: April 2003 - Volume 26 - Issue 2 - p 107–111

Because no consensus exists regarding recommendable dose levels for irinotecan, an intrapatient dose escalation phase I-II study was initiated in previously treated patients with colorectal cancer. Survival was a secondary endpoint. Thirty-five consecutive patients with progressive disease after 5-fluorouracilbased chemotherapy were enrolled to receive irinotecan starting from 250 mg/m2/3 weeks and rising to currently used therapeutic doses. In total, 162 cycles were administered. The median tolerable dose was 250 mg/m2. Twelve patients (34%) were unable to tolerate doses greater than 250 mg/m2, 10 patients (28%) presented toxicity at 250 mg/m2 and 2 patients tolerated only 200 mg/m2. Three patients (9%) had partial response. The major adverse reactions were grade III-IV diarrhea, grade II-III nausea/vomiting, grade II-III neutropenia, and grade II-III anaemia in 28%, 48%, 11%, and 17% of the patients, respectively. Median survival time and time to progression were 8 and 3 months, respectively. The current irinotecan dose of 350 mg/m2/3 weeks appears unacceptably toxic and, hence, a lower dose needs to be considered. The response rates obtained are similar to the results observed in phase III studies, and its activity appears not to be adversely affected with this treatment scheme.

From the Servicio de Oncología Médica, Hospital General de Asturias, Oviedo, Spain.

Address correspondence and reprint requests to Dr. Jose M. Vieitez, Servicio de Oncología Médica, Hospital General de Asturias, C/Julian Claveria SN, 33006 Oviedo (Asturias), Spain. E-mail:

© 2003 Lippincott Williams & Wilkins, Inc.