To evaluate the efficacy and safety of raltitrexed combind with irinotecan in patients with metastatic colorectal cancer (mCRC).

Between January 2015 and December 2018, a total of 34 patients with mCRC after the failure of first-line or second-line chemotherapy were selected and treated with raltitrexed plus irinotecan in Cancer Hospital Chinese Academy of Medical Sciences. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progress-free survival (PFS), overall survival (OS) and safety.

The pathology of 34 patients was adenocarcinoma. There were 16 patients (47.1%) with rectal cancer, followed by 10 cases (29.4%) in the left colon and 8 cases (23.5%) in the right colon. Thirty patients (88.2%) accepted undergone surgical treatment. Six achieved a partial response (PR), Twenty-five had a stable disease (SD) and 3 had a progressive disease (PD). The ORR was 17.6% (6/34), and the DCR was 91.2% (31/34). For second-line treatment, the ORR was 21.7% (5/23), DCR was 91.3% (21/23). For third-line treatment, the ORR was 9.1% (1/11), DCR was 90.9% (10/11). All patients were defined progression of disease, the median progression free survival (mPFS) was 180 days(95% CI: 157.2~202.8). The median overall survival (mOS) was not observed at the last follow-up. The average OS was (389±51.1)days. the median PFS of patients receiving second-line treatment was 193 days, with an average OS of (412±61.5)days. Patients receiving third-line treatment had mPFS of 150 days and mOS of 311 days. The levels of tumor markers CEA and CA19-9 decreased after treatment. The average levels of CA19-9 before and after treatment were 169.8±48.0 U/mL and 143.8±57.7 U/mL (t=0.700, P=0.655). The average level of CEA before treatment was (255.0±40.6) ng/mL and (104.2±32.4) ng/mL after treatment, the decline has statistically significant (t=1.759, P=0.001). The main adverse reactions were nausea, vomiting, diarrhea, leucopenia, neutropenia, hemoglobin reduction and transaminase elevation, mostly grade I or II. Grade III adverse reactions included leucopenia (2/34), anemia (1/34) and transaminase elevation (1/34). There were no grade IV adverse reactions and treatment-related deaths.

The combination of raltitrexed combined with irinotecanas second-line and above treatment could be an efficient and safe option for patients with mCRC. Particularly, it has presented encouraging ORR and lower toxicities as second-line therapy, which is worthy of further clinical application.