Goro Nakayama1, Nao Takano2, Hiroya Taniguchi3, Kiyoshi Ishigure4, Hiroyuki Yokoyama5, Hitoshi Teramoto6, Ryoji Hashimoto7, Mitsuru Sakai8, Akiharu Ishiyama9, Takashi Kinoshita10, Naomi Hayashi11, Masanori Nakamura4, Norifumi Hattori12, Yusuke Sato12, Shinichi Umeda12, Kei Uehara12, Toshisada Aiba12, Fuminori Sonohara12, Masamichi Hayashi12, Mitsuro Kanda12, Daisuke Kobayashi5, Chie Tanaka12, Suguru Yamada12, Masahiko Koike12, Michitaka Fujiwara12, Kenta Murotani13, Masahiko Ando14, Yuichi Ando15, Kei Muro16, Yasuhiro Kodera12. 1. Department of Gastroenterological Surgery, Nagoya University Hospital, Nagoya, Japan. Electronic address: goro@med.nagoya-u.ac.jp. 2. Department of Surgery, Tokai Central Hospital, Kagamihara, Japan. 3. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 4. Department of Surgery, Konan Kosei Hospital, Konan, Japan. 5. Department of Surgery, Komaki City Hospital, Komaki, Japan. 6. Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan. 7. Department of Surgery, Nakatsugawa Municipal Hospital, Nakatsugawa, Japan. 8. Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan. 9. Department of Surgery, Okazaki City Hospital, Okazaki, Japan. 10. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. 11. Department of Medical Oncology, Cancer Institute Hospital, Tokyo, Japan. 12. Department of Gastroenterological Surgery, Nagoya University Hospital, Nagoya, Japan. 13. Biostatistics Center, Kurume University, Kurume, Japan. 14. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan. 15. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan. 16. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Abstract
BACKGROUND: Peripheral sensory neuropathy (PSN) caused by oxaliplatin-based adjuvant chemotherapy adversely affects patients' quality of life. This study evaluated the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) with intermittent oxaliplatin use compared with the standard CAPOX in adjuvant therapy for colon cancer. PATIENTS AND METHODS: Patients with curative resection for stage II/III colon cancer were randomly assigned to receive either CAPOX with continuous oxaliplatin (eight cycles of CAPOX) or CAPOX with intermittent oxaliplatin (two cycles of CAPOX, four cycles of capecitabine and two cycles of CAPOX). The primary end-point was the 1-year PSN rate, and the key secondary end-point was disease-free survival (DFS). RESULTS:Two hundred patients were enrolled in the intent-to-treat population. After 4 patients withdrew, 196 patients were included in the safety analysis. The overall treatment completion rate was 65% for continuous vs. 89% for intermittent treatment (p < 0.001). The 1-year PSN rate was 60% (95% confidence interval [CI], 50%-70%) for continuous and 16% (95% CI, 10%-25%) for intermittent treatment (p < 0.001). After a median follow-up of 52 months, 40 events (20%) were observed. The 3-year DFS was 81% (95% CI, 71%-87%) for continuous and 84% (95% CI, 75%-90%) for intermittent treatment (hazard ratio [HR], 0.87; 95% CI, 0.47-1.63). Among patients with high-risk disease (T4 or N2-3), the 3-year DFS was 57% for continuous vs. 74% for intermittent treatment (HR, 0.66). CONCLUSION:CAPOX with planned intermittent oxaliplatin may be feasible as an adjuvant therapy for colon cancer and substantially reduce the duration of long-lasting PSN. TRIAL IDENTIFIER: UMIN000012535.
RCT Entities:
BACKGROUND:Peripheral sensory neuropathy (PSN) caused by oxaliplatin-based adjuvant chemotherapy adversely affects patients' quality of life. This study evaluated the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) with intermittent oxaliplatin use compared with the standard CAPOX in adjuvant therapy for colon cancer. PATIENTS AND METHODS: Patients with curative resection for stage II/III colon cancer were randomly assigned to receive either CAPOX with continuous oxaliplatin (eight cycles of CAPOX) or CAPOX with intermittent oxaliplatin (two cycles of CAPOX, four cycles of capecitabine and two cycles of CAPOX). The primary end-point was the 1-year PSN rate, and the key secondary end-point was disease-free survival (DFS). RESULTS: Two hundred patients were enrolled in the intent-to-treat population. After 4 patients withdrew, 196 patients were included in the safety analysis. The overall treatment completion rate was 65% for continuous vs. 89% for intermittent treatment (p < 0.001). The 1-year PSN rate was 60% (95% confidence interval [CI], 50%-70%) for continuous and 16% (95% CI, 10%-25%) for intermittent treatment (p < 0.001). After a median follow-up of 52 months, 40 events (20%) were observed. The 3-year DFS was 81% (95% CI, 71%-87%) for continuous and 84% (95% CI, 75%-90%) for intermittent treatment (hazard ratio [HR], 0.87; 95% CI, 0.47-1.63). Among patients with high-risk disease (T4 or N2-3), the 3-year DFS was 57% for continuous vs. 74% for intermittent treatment (HR, 0.66). CONCLUSION: CAPOX with planned intermittent oxaliplatin may be feasible as an adjuvant therapy for colon cancer and substantially reduce the duration of long-lasting PSN. TRIAL IDENTIFIER: UMIN000012535.