Randomised phase II trial of capecitabine plus oxaliplatin with continuous versus intermittent use of oxaliplatin as adjuvant chemotherapy for stage II/III colon cancer (CCOG-1302 study).

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.

Informations de copyright

Copyright © 2020. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest statement G.N. reports receiving honoraria from Chugai, Janssen, Yakult Honsha, Taiho, Eli Lilly, Miyarinsan and Takeda and research funding to his institution from Eli Lilly, outside the submitted work. H.T. reports receiving honoraria from Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MBL, Merck Bio Pharma, Mitsubishi Tanabe Pharma, MSD, Nippon Kayaku, Novartis, Sanofi, Taiho, Takeda and Yakult Honsha and research funding to his institution from Daiichi Sankyo, Isofol, MSD, Novartis, Ono, Pfizer, Sumitomo Dainippon Pharma, Sysmex and Takeda, outside the submitted work. K.U. reports receiving honoraria from Eli Lilly and Chugai, outside the submitted work. K.M. reports receiving honoraria from Chugai, outside the submitted work. M.A. reports receiving grant from Kyowa Kirin, outside the submitted work. Y.A. reports receiving grants and personal fees from Chugai, Kyowa Hakko Kirin, Nippon Kayaku, Yakult Honsha, Mochida, Ono, Taiho and Daiichi Sankyo; personal fees from Eli Lilly, Novartis, Bayer, Bristol-Myers Squibb, Sawai, Tsumura and Shionogi and grants from Eisai, outside the submitted work. K.M. reports receiving grants from Daiichi Sankyo, Parexel International, Shionogi Pharma, Sumitomo Dainippon, MSD, Pfizer, Mediscience Planning and Solasia Pharma; grants and personal fees from Ono and Sanofi and personal fees from Takeda, Taiho, Bristol-Myers Squibb, Bayer, Eli Lilly and Chugai, outside the submitted work. Y.K. reports receiving honoraria from Taiho, Ono, Daiichi Sankyo, Eli Lilly, Chugai, Yakult Honsha, MSD, Nippon Kayaku, Sawai, Tsumura and Miyarinsan and research funding to his institution from Taiho, Chugai, Eli Lilly, Sanofi, Nippon Kayaku, Ono, Otsuka, Takeda, MSD and Pfizer, outside the submitted work.