Purpose: Fewer treatment options are available for refractory metastatic colorectal cancer (mCRC). In early trials, S-1 monotherapy was effective for mCRC patients after chemotherapy failure and its combination with oral leucovorin therapy offers promising results in untreated mCRC. Hence, we conduct a Phase II trial to assess the efficacy of S-1 plus oral leucovorin (SL) in refractory mCRC that progressed after multiple prior standard therapies. Methods: In this open-label, single-arm study, we enrolled the refractory mCRC patients who received fluoropyrimidine, oxaliplatin, and irinotecan treatment and at least one targeted therapy previously. The doses of SL were 40–60 and 30 mg twice daily separately. They were administered for 7 days in a 2-week cycle. Treatment was continued until disease progression. Results: Of the 41 enrolled patients, 36 patients were evaluable with 61.1% disease control rate. The median progression-free survival and overall survival were 2.55 and 7.63 months, respectively. Regression change in tumor size stayed 10%–20% in five patients (13.9%) through 18 weeks after treatment, and two patients continued free from tumor progression at 30 and 42 weeks. Compared with moderate heavily pretreated mCRC patient subgroup (≤4 prior regimens), the severe heavily pretreated subgroup (≥5 prior regimens) showed similar disease control rate and survival benefit. Grade 3 or higher toxicities were documented only in 11 patients (26.8%). Conclusion: SL shows potential as a salvage regimen in refractory mCRC patients especially in the severe heavily pretreated setting and is well tolerated in these patients.
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