title: Phase I study assessing the feasibility of the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  The objective of this study was to determine the recommended dose (RD) of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma.
  
  
  METHODS
  This phase I study used a traditional "3+3" dose-escalation design, with four dose levels. A dose-escalation schedule consisted of two doses of S-1 (60 and 80 mg/m(2) twice daily) for 2 weeks in alternate-day administration, three doses of irinotecan (125, 150, and 180 mg/m(2)) on day 1, and a single dose of oxaliplatin (85 mg/m(2)) on day 1 of a 2-week cycle. Dose-limiting toxicities (DLTs) were assessed in the first four cycles to determine the maximum tolerated dose. This clinical study was registered at UMIN000014339.
  
  
  RESULTS
  Fifteen patients received this regimen (median, eight cycles; range 4-12). At dose level 3 (S-1, 80 mg/m(2); irinotecan, 150 mg/m(2)), 2/6 patients experienced DLTs of grade 3 fatigue and grade 4 neutropenia. At dose level 4, all three patients experienced DLTs: grade 3 fatigue (n = 1) and grade 4 neutropenia (n = 2). The RD was 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively. We found the following: response rate, 47 %; disease control rate, 80%; median progression-free survival, 6.7 months; overall survival, 13.4 months.
  
  
  CONCLUSIONS
  The SOXIRI regimen's RD is 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively.
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan. satoi@hirakata.kmu.ac.jp.
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Akahori
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirooka
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Yamaki
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kotsuka
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ryota
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiwada
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Department of Surgery, Nara Prefectural Seiwa Medical Center, Nara, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin
keywords: Irinotecan; Oxaliplatin; Phase I study; S-1; Unresectable pancreatic ductal adenocarcinoma