A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2014-04, Vol.17 (2), p.354-361
• Main Authors: Moriwaki, Toshikazu, Hirai, Shinji, Hironaka, Shuichi, Amagai, Kenji, Soeda, Atsuko, Sato, Mikio, Nihei, Takeshi, Hirose, Mitsuaki, Matsuda, Kenji, Ohkawara, Atsushi, Yamaguchi, Taketo, Ozeki, Mitsuharu, Mamiya, Takashi, Murashita, Tetsuya, Hyodo, Ichinosuke
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastric cancer; Gastroenterology; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oncology; Original Article; Oxonic Acid - administration & dosage; Prognosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Surgical Oncology; Survival Rate; Taxoids - administration & dosage; Tegafur - administration & dosage; Young Adult
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-013-0284-4

Background S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients. Methods In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80–120 mg according to body surface area on days 1–14, and cisplatin 20 mg/m 2 i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate. Results Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36–86 %] and 53 % (95 % CI, 30–75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9–14.6 months) and 15.7 months (4.0–27.4 months), respectively ( P  = 0.064). Progression-free survival was significantly shorter in the SWP arm than in the SP arm ( P  = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression. Conclusions No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.