To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer.

An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer. The outcomes included overall survival, overall response rate and toxicities.

This meta-analysis included 11 studies with 4622 patients. Overall, there were no significant differences between the two regimens in terms of overall survival (HR=1.06, 95% CI: 0.96–1.17, P=0.23) or overall response rate (RR=1.09, 95% CI: 0.86–1.38, P=0.47). In subgroup analysis, patients in raltitrexed/oxaliplatin group had significantly higher partial response (RR=1.53, 95% CI: 1.17–2.00, P=0.002), overall response rate (RR=1.42, 95% CI: 1.10–1.82, P=0.006), disease control rate (RR=1.16, 95% CI: 1.04–1.29, P=0.009) and lower progressive disease (RR=0.61, 95% CI: 0.45–0.84, P=0.002) when compared to 5-fluorouracil/leucovorin/oxaliplatin group. Occurrence of severe anemia (RR=2.23, 95% CI: 1.38–3.59, P=0.0001), asthenia (RR=2.29, 95% CI: 1.36–3.84, P=0.002), hepatic disorders (RR=7.51, 95% CI: 1.30–43.56, P=0.02), and nausea/vomit (RR=1.70, 95% CI: 1.03–2.81, P=0.04) were significantly higher with the raltitrexed arm treatment, while frequencies of grade 3/4 alopecia (RR=0.36, 95% CI: 0.26–0.50, P<0.00001) and stomatitis/mucositis (RR=0.14, 95% CI: 0.07–0.31, P<0.00001) were increased in the 5-fluorouracil group.

Raltitrexed-based chemotherapy regimen leads to an equivalent overall survival and response rates with acceptable toxicities compared to traditional 5-fluorouracil-based regimen in patients with advanced colorectal cancer. Raltitrexed can be a treatment option for these patients when 5-fluorouracil-based regimens are not tolerated or inappropriate.