Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003)

• Published in: International journal of clinical oncology Vol. 22; no. 6; pp. 1052 - 1059
• Main Authors: Tanaka, Hiroaki, Kanda, Mitsuro, Morita, Satoshi, Taguri, Masataka, Nishikawa, Kazuhiro, Shimada, Mitsuo, Muguruma, Kazuya, Koeda, Keisuke, Takahashi, Masazumi, Nakamori, Mikihito, Konno, Hiroyuki, Tsuji, Akihito, Hosoya, Yoshinori, Shirasaka, Tetsuhiko, Yamamitsu, Susumu, Sowa, Michio, Kitajima, Masaki, Okajima, Masazumi, Kobayashi, Michiya, Sakamoto, Junichi, Saji, Shigetoyo, Hirakawa, Kosei
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.12.2017; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Cancer Research; Cancer therapies; Chemotherapy; Clinical trials; Disease control; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gastric cancer; Humans; Japan; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality; Surgical Oncology; Survival; Tegafur - administration & dosage; Tegafur - adverse effects; Treatment Outcome; Chemotherapy; Gastric cancer; S-1; Randomized phase II study
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-017-1157-3

Purpose Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. Methods 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m 2 /day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. Results The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% ( p  = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold ( p  = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15–2.68, p  = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97–2.29, p  = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively ( p  = 0.007). Conclusion The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.