A prospective phase II study of raltitrexed combined with S‐1 as salvage treatment for patients with refractory metastatic colorectal cancer

AIM: A third‐line chemotherapy regimen for metastatic colorectal cancer (mCRC) is not available in China. Studies have shown that raltitrexed or S‐1 has no complete cross‐resistance with fluorouracil (5‐FU). In this phase II study, we prospectively analyzed the efficacy and safety of raltitrexed combined with S‐1 (RS regimen) in the treatment of mCRC after the failure of conventional chemotherapy. METHODS: A total of 105 patients with mCRC with progression following treatment with 5‐FU, oxaliplatin, and irinotecan were enrolled between November 2015 and May 2019. Patients received intravenous infusion of raltitrexed (3 mg/m(2) from day 1 every 3 weeks) and oral S‐1 (80‐120 mg for 14 days every 3 weeks). Tumor evaluations were performed every two cycles according to the RECIST 1.1 guidelines. RESULTS: In the intention‐to‐treat patients, the objective response and disease control rates were 7.62% and 48.57%, respectively. The median progression‐free survival and median overall survival were 2.5 and 8.0 months, respectively. Common adverse events included neutropenia, anemia, thrombocytopenia, and nausea, while neutropenia, anemia, thrombocytopenia nausea, diarrhea, skin eruption, and oral ulceration had grade 3 or higher adverse events. Subgroup analysis revealed that primary site or gene mutation status had little influence on the RS regimen efficacy, while the baseline albumin level, 5‐FU administration in second‐line therapy, and number of previous treatment regimens affected the efficacy. CONCLUSION: The RS regimen demonstrated favorable effects in patients with mCRC following failure of standard chemotherapy, and could be a new choice for third‐line treatment, and must be verified in future randomized clinical trials (Clinical trial: NCT02618356).