A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer

• Published in: Cancer chemotherapy and pharmacology 2016-11, Vol.78 (5), p.949-958
• Main Authors: Han, Boram, Jung, Joo Young, Kim, Hyeong Su, Cho, Ji Woong, Kim, Kab Choong, Lim, Hyun, Kang, Ho Suk, Ha, Hong Il, Kim, Min-Jeong, Kim, Jung Hoon, Choi, Dae Ro, Jang, Geundoo, Kim, Jung Han, Song, Hunho, Zang, Dae Young
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Agents - administration & dosage; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Cancer Research; Dose-Response Relationship, Drug; Drug Combinations; Female; Gastrointestinal Neoplasms - drug therapy; Humans; Male; Maximum Tolerated Dose; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Oncology; Organoplatinum Compounds - administration & dosage; Original Article; Oxonic Acid - administration & dosage; Pharmacology/Toxicology; Tegafur - administration & dosage; Treatment Outcome
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-016-3147-y

Purposes To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer. Methods Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1–7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m 2 ; level 2, 85/120/80 mg/m 2 ; level 3, 85/120/100 mg/m 2 ; level 4, 85/150/100 mg/m 2 ; and level 5, 85/180/100 mg/m 2 . Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity. Results Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %. Conclusions The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m 2 of oxaliplatin, 180 mg/m 2 of irinotecan, and 100 mg/m 2 of S-1 every 2 weeks.