title: A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer.
abstract: OBJECTIVE
  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/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; and level 5, 85/180/100 mg/m2. 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/m2of oxaliplatin, 180 mg/m2of irinotecan, and 100 mg/m2of S-1 every 2 weeks.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Han
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Hyeong Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Surgery, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Cho
authors.affiliation: Department of Surgery, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Kab Choong
authors.initials: KC
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Ho Suk
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Department of Radiology, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Hong Il
authors.initials: HI
authors.lastname: Ha
authors.affiliation: Department of Radiology, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Dae Ro
authors.initials: DR
authors.lastname: Choi
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Geundoo
authors.initials: G
authors.lastname: Jang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea.
authors.forename: Hunho
authors.initials: H
authors.lastname: Song
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, 14068, Republic of Korea. fhdzang@hallym.ac.kr.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Zang
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin
keywords: Gastrointestinal cancer; Irinotecan; Maximum tolerated dose; Oxaliplatin; S-1