Hiroki Yamaue1, Atsushi Shimizu2, Yasuhiro Hagiwara3, Masayuki Sho4, Hiroaki Yanagimoto5, Shoji Nakamori6, Hideki Ueno7, Hiroshi Ishii8, Masayuki Kitano9, Kazuya Sugimori10, Hiroyuki Maguchi11, Shinichi Ohkawa12, Hiroshi Imaoka13, Daisuke Hashimoto14, Kazuki Ueda15, Hiroko Nebiki16, Tatsuya Nagakawa17, Hiroyuki Isayama18, Isao Yokota19, Yasuo Ohashi20, Tetsuhiko Shirasaka21. 1. Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama, 641-8510, Japan. yamaue-h@wakayama-med.ac.jp. 2. Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama, 641-8510, Japan. 3. Department of Biostatistics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. 4. Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. 5. Department of Surgery, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1010, Japan. 6. Department of Surgery, Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan. 7. National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 8. Clinical Research Center, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-machi, Matsuyama City, Ehime, 791-0280, Japan. 9. Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan. 10. Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. 11. Center for Gastroenterology, Teine-Keijinkai Hospital, 1-40 Maeda 1-jo 12-chome, Teine-ku, Sapporo, 006-8555, Japan. 12. Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. 13. Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. 14. Department of Gastroenterological Surgery, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. 15. Second Department of Internal Medicine y, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama, 641-8510, Japan. 16. Department of Gastroenterology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori Miyakojima-ku, Osaka, 543-0021, Japan. 17. 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. 18. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 19. Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. 20. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan. 21. Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Abstract
PURPOSE: 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). METHODS: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. RESULTS: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. CONCLUSION: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.
RCT Entities:
PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
Alternate-day treatment; EORTC QLQ-30; EQ-5D; S-1; Unresectable pancreatic cancer