A single-arm phase II trial of

Background: There is an unmet need for optimal third- or later-line treatment options for refractory or metastatic colorectal cancer (mCRC) patients. This phase II study investigated whether high-dose irinotecan rechallenge based on Methods: Patients who had previously received more than two lines of chemotherapy, including 5-fluorouracil, oxaliplatin, irinotecan and had shown either a partial response or durable response for more than 24 weeks to irinotecan were included. Patients without the defective allele of Results: A total of 32 patients was enrolled between October 2020 and March 2023. The primary endpoint, 12w DCR was 40.6% (13 of 32 patients). The ORR was 15.6% (5 of 32). The median OS was 9.3 months (95% CI, 5.3 to 13.3) and the median PFS was 2.9 months (95% CI, 2.5 to 3.3). Grade 3 or higher adverse events were observed in 19 patients (59.4%). Dose reduction due to adverse events occurred in 9 patients (50.0%) in Conclusion: High-dose irinotecan rechallenge guided by UGT1A1 genotype was feasible and showed meaningful disease control in third-line or later settings for mCRC patients previously responsive to irinotecan.