M-H Ryu1, E Baba2, K H Lee3, Y I Park4, N Boku5, I Hyodo6, B-H Nam7, T Esaki8, C Yoo1, B-Y Ryoo1, E-K Song9, S-H Cho10, W K Kang11, S H Yang12, D Y Zang13, D B Shin14, S R Park1, K Shinozaki15, T Takano16, Y-K Kang17. 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 2. Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Department of Hemato-oncology, Yeungnam University Hospital, Daegu. 4. Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea. 5. Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki. 6. Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan. 7. Biometric Research Branch, National Cancer Center, Goyang, Gyeonggi, Korea. 8. Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Fukuoka, Japan. 9. Division of Hematology/Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju. 10. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Gwangju. 11. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School Medicine, Seoul. 12. Department of Internal Medicine, Korea Cancer Center Hospital, Seoul. 13. Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang. 14. Division of Hematology/Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea. 15. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima. 16. Department of Medical Oncology, Toranomon Hospital, Minato-ku, Japan. 17. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ykkang@amc.seoul.kr.
Abstract
BACKGROUND:Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS:Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.
RCT Entities:
BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS:SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.
Authors: Dong-Hoe Koo; Min-Hee Ryu; Mi-Yeon Lee; Heejung Chae; Eo Jin Kim; Mee-Sun Moon; Yoon-Koo Kang Journal: Cancer Res Treat Date: 2020-10-06 Impact factor: 4.679