title: A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer.
abstract: OBJECTIVE
  In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).
  
  
  METHODS
  Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized.
  
  
  RESULTS
  Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline.
  
  
  CONCLUSIONS
  RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Nakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isayama
authors.forename: Kei
authors.initials: K
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naminatsu
authors.initials: N
authors.lastname: Takahara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamada
authors.forename: Suguru
authors.initials: S
authors.lastname: Mizuno
authors.forename: Koji
authors.initials: K
authors.lastname: Miyabayashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Dai
authors.initials: D
authors.lastname: Mohri
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kogure
authors.forename: Natsuyo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirano
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ijichi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002955:Leucovorin; D000093542:Gemcitabine