Tomomi Kashiwada1,2, Katsunori Shinozaki3, Shohei Ueno4, Hirofumi Kawanaka5, Futoshi Uno6, Yoshihiro Okita7, Masaru Fukahori8, Hidenobu Matsushita9, Yasunori Emi10, Mototsugu Shimokawa11,12, Akitaka Makiyama4,13, Hiroshi Saeki14, Eiji Oki15, Yoshihiko Maehara16, Masaki Mori17, Eishi Baba18. 1. Division Hematology, Respiratory Medical and Oncology, Department of Medical Oncology, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. 2. Saga Medical Center Koseikan, 400 Kasemachi, Nakabaru, Saga City, Saga, 849-8571, Japan. 3. Division of Clinical Oncology, Hirosima Prefectural Hospital, Hirosima, Japan. 4. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. 5. Clinical Research Institute and Department of Surgery, National Hospital Organization, Beppu Medical Center, Beppu, Japan. 6. Department of Surgery, Okayama Rosai Hospital, Okayama, Japan. 7. Kagawa University Hospital Cancer Center, Takamatsu, Japan. 8. Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Japan. 9. Department of Surgery, Tosei General Hospital, Seto, Japan. 10. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan. 11. Department of Biostatistics, Cancer Biostatistics Laboratory, Yamaguchi University Graduate School of Medicine, Clinical Research Institute, Yamaguchi, Japan. 12. National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 13. Cancer Center, Gifu University Hospital, Gifu, Japan. 14. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan. 15. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. okieiji@surg2.med.kyushu-u.ac.jp. 16. Department of Surgery, Kyushu Central Hospital of the Mutual Aid Association of PublicSchool Teachers, Fukuoka, Japan. 17. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 18. Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND: In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) in AGC. METHODS:Patients with HER2-negative AGC received 80 mg/m2/day S-1 orally on days 1-14 and 130 mg/m2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0. RESULTS:Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%). CONCLUSIONS: This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.
RCT Entities:
BACKGROUND: In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) in AGC. METHODS:Patients with HER2-negative AGC received 80 mg/m2/day S-1 orally on days 1-14 and 130 mg/m2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0. RESULTS: Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%). CONCLUSIONS: This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162