Phase I/II study of a 3‐week cycle of irinotecan and S‐1 in patients with advanced colorectal cancer

• Published in: Cancer science 2010-12, Vol.101 (12), p.2591-2595
• Main Authors: Kusaba, Hitoshi, Esaki, Taito, Futami, Kitaro, Tanaka, Sinnosuke, Fujishima, Hiromitsu, Mitsugi, Kenji, Sakai, Kenji, Ariyama, Hiroshi, Tanaka, Risa, Kinugawa, Naoko, Ueki, Takashi, Mibu, Rhuichi, Baba, Eishi, Nakano, Shuji, Akashi, Koichi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Irinotecan; Kaplan-Meier Estimate; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Neoplasm Staging; Original; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tegafur - administration & dosage; Tegafur - adverse effects; Tumors
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01728.x

The combination of an oral fluoropyrimidine derivative, S‐1, and irinotecan is expected to be a promising regimen for advanced colorectal cancer. This study was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with S‐1 in a 3‐week cycle regimen and to observe the safety and efficacy for patients with previously untreated advanced colorectal cancer. Eighty milligrams per m2 of S‐1 was given orally for 14 consecutive days and escalated doses of irinotecan were administered on days 1 and 8 every 3 weeks in the phase I trial. Forty patients were treated at the RD during the phase II trial. Forty‐three patients were enrolled between February 2005 and March 2007. The dose‐limiting toxicity was diarrhea and abdominal pain. The MTD of irinotecan was 100 mg/m2 and the RD was determined to be 80 mg/m2 of irinotecan combined with 80 mg/m2 of S‐1. The phase II trial showed that 22 of 40 patients achieved a complete or partial response and eight had stable disease. The overall response rate was 55.0%. The median progression‐free survival time and median survival time were 6.7 and 21 months, respectively. There were no treatment‐related deaths. The main toxicities were leukopenia, neutropenia, anorexia and diarrhea. This study suggests the combination of irinotecan and S‐1 repeated every 3 weeks is tolerable and effective for patients with previously untreated advanced colorectal cancer. (Cancer Sci 2010; 101: 2591–2595)