title: Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer.
abstract: Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604).
  
  
  
  Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety.
  
  
  
  A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment.
  
  
  
  S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.
authors.affiliation: Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama, 641-8510, Japan. yamaue-h@wakayama-med.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
authors.affiliation: Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Biostatistics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hagiwara
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
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, Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.affiliation: Clinical Research Center, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-machi, Matsuyama City, Ehime, 791-0280, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitano
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sugimori
authors.affiliation: Center for Gastroenterology, Teine-Keijinkai Hospital, 1-40 Maeda 1-jo 12-chome, Teine-ku, Sapporo, 006-8555, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maguchi
authors.affiliation: Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imaoka
authors.affiliation: Department of Gastroenterological Surgery, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Second Department of Internal Medicine y, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama, 641-8510, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Gastroenterology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori Miyakojima-ku, Osaka, 543-0021, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nebiki
authors.affiliation: Department of Gastroenterology, Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital, 8-5 Kita 2 Jou Higashi, Chuo-ku, Sapporo, 060-0033, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nagakawa
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: Hiroyuki
authors.initials: H
authors.lastname: Isayama
authors.affiliation: Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Yokota
authors.affiliation: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000523:psychology; D011446:Prospective Studies; D011788:Quality of Life; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D044465:White People
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid
keywords: Alternate-day treatment; EORTC QLQ-30; EQ-5D; S-1; Unresectable pancreatic cancer