Adjuvant CAPOX (capecitabine plus oxaliplatin) provided significant disease-free survival (DFS) benefit in patients with high-risk stage Ⅱor stage Ⅲ colorectal cancer (CRC), which might translate into long-term overall survival (OS). However, the standard triweekly CAPOX has recently raised some concerns onits hematological toxicity such as thrombocytopenia, which results in discontinuation ofadjuvant courses in a majority of patients. The regimen of modified biweekly CAPOX was observed to be generally well-tolerated in previous studies.
We conducted a prospective, phase II study to investigate the efficacy and safety between these two adjuvant chemotherapy models. Patients were randomized (1:1) to receive capecitabine 1000mg/m2 BID D1-D14 with oxaliplatin 130mg/m2 IV D1, Q21 days(standard triweekly arm) or capecitabine 1000mg/m2 BID D1-D10 with oxaliplatin 85mg/m2 IV D1, Q14 days (modifiedbiweeklyarm) as adjuvant therapy. Patients with T3N1M0 disease would receive 3 months of adjuvant chemotherapy while patients who had T4 or N2 disease would receive 6 months of adjuvant chemotherapy. The primary endpoint was DFSwhile safety and OS were secondary endpoints.
Since the enrollment of the first patient on June 28, 2018, 85 patients have been enrolled, 59 of whom have completely completed adjuvant therapy, 20 patients are still in treatment, and 6 patients terminated the treatment due to personal reasons, adverse reactions intolerant or postoperative complications such as intestinal adhesion. Of the 59 patients who completed adjuvant therapy, 29 received the triweekly regimen and 30 received the biweekly regimen, respectively. Leukopenia was 43% in the biweekly group and 58% in the triweekly group. Thrombocytopenia was 33% at biweekly group, 51% at triweekly group. Peripheral neurotoxicity was 46% at biweekly group, and 75% at triweekly group.
Adverse events Grade Case No. Biweekly XELOX Triweekly XELOX WBC I 9 6 II 3 43% 10 58% III 1 1 PLT I 4 7 II 3 33% 6 51% III 3 2 Hb I 9. 36% 5 20% II 2 1 Liver function injury I 2. 16% 5 31% II 3 4 Peripheral neurotoxicity I 7 10 II 3 46% 5 75% III 4 7
Blood toxicity was significantly reduced in the biweekly treatment group, as were liver function injury and neurotoxicity.DFS and OS are not available for the time being due to immature data.
The authors.
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All authors have declared no conflicts of interest.