Yukinori Kurokawa1, Jin Matsuyama2, Kazuhiro Nishikawa3, Atsushi Takeno4, Yutaka Kimura5, Kazumasa Fujitani6, Ryohei Kawabata7, Yoichi Makari8, Tetsuji Terazawa9, Hisato Kawakami10, Daisuke Sakai11, Toshio Shimokawa12, Taroh Satoh11. 1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan. ykurokawa@gesurg.med.osaka-u.ac.jp. 2. Department of Surgery, Yao Municipal Hospital, Osaka, Japan. 3. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. 4. Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan. 5. Department of Surgery, Sakai City Medical Center, Osaka, Japan. 6. Department of Surgery, Osaka General Medical Center, Osaka, Japan. 7. Department of Surgery, Osaka Rosai Hospital, Osaka, Japan. 8. Department of Surgery, Minoh City Hospital, Osaka, Japan. 9. Cancer Chemotherapy Center, Osaka Medical College, Osaka, Japan. 10. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan. 11. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan. 12. Clinical Study Support Center, Wakayama Medical University, Wakayama, Japan.
Abstract
BACKGROUND: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. METHODS: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80-120 mg on days 1-14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80-120 mg on days 1-21, every 5 weeks). The primary endpoint was overall survival (OS). RESULTS: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2-49) with DS and 5.5 (range 1-10) with CS. There were no treatment-related deaths. The most common grade 3-4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337-1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). CONCLUSIONS: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.
BACKGROUND: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. METHODS: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80-120 mg on days 1-14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80-120 mg on days 1-21, every 5 weeks). The primary endpoint was overall survival (OS). RESULTS: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2-49) with DS and 5.5 (range 1-10) with CS. There were no treatment-related deaths. The most common grade 3-4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337-1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). CONCLUSIONS: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.