Safety and feasibility of S-1 after capecitabine-induced toxicity in the adjuvant treatment of colon cancer patients: A population-based real-world study

BACKGROUND: S-1 has comparable efficacy to capecitabine/5-FU in metastatic colorectal cancer, but is associated with a lower incidence of hand-foot syndrome (HFS) and cardiovascular toxicity (CVT). The European Medicines Agency has approved its use when capecitabine or 5-FU is discontinued due to HFS or CVT. However, in the adjuvant setting, data on its safety profile are scarce. We assessed the feasibility of S-1 in patients who discontinued capecitabine due to HFS or CVT.

METHODS: We included all patients with colon cancer included in the Prospective Dutch Colorectal Cancer Cohort (PLCRC), who switched from capecitabine to S-1 due to HFS or CVT, in the adjuvant treatment setting between March 2018 and May 2025. We assessed the completion rate of adjuvant treatment as well as toxicity following switch to S-1.

RESULTS: A total of 55 patients with colon cancer were analyzed. Reason to switch from capecitabine to S-1 was HFS in 42 % (n = 23) and CVT in 53 % (n = 29) of patients. 91 % (n = 21) of patients who switched to S-1 for HFS and 97 % (n = 28) for CVT experienced a lower grade or complete resolution of symptoms. 80 % (n = 44) of patients were able to complete adjuvant treatment after the switch. Persistent HFS led to early discontinuation in 9 % (2/23), with no discontinuation due to CVT recurrence.

CONCLUSION: S-1 is a feasible and useful alternative for patients with colon cancer experiencing capecitabine-induced HFS or CVT in the adjuvant setting and allows the continuation of potentially curative fluoropyrimidine-based treatment.