The review included four RCTs (n=1,960) and four phase II studies (n=371; 306 evaluable).
Survival time: the pooled median survival time, based on four RCTs (n=1,965), was 10.2 months for raltitrexed and 11.2 months for 5-FU plus leucovorin.
Response rates: the pooled response rate showed no statistically significant difference between raltitrexed and 5-FU plus leucovorin (odds ratio 0.95, 95% CI: 0.76, 1.19). Four phase II studies of raltitrexed (n=306) reported response rates ranging from 24 to 56%. Two reported median survival times of 11.8 and 11.2 months.
Qualify of life: quality of life data were available from three RCTs. One trial reported statistically significant benefits with raltitrexed over 5-FU plus leucovorin in quality of life dimensions at week 2, but not at weeks 5 or 15. The only significant difference in one other trial was in the impact of nausea and vomiting; this was apparently greater with raltitrexed. In the third trial, quality of life at 12 weeks was significantly worse with raltitrexed for several components, including nausea and vomiting.
Adverse effects: seven RCTs and one phase II study reported adverse effects. The preliminary results from one randomised trial (n=604) reported 12 treatment-related deaths with raltitrexed and none with 5-FU plus leucovorin. Another randomised trial (n=433), which used the Symptom Checklist, found that toxicity was significantly lower overall for raltitrexed compared with 5-FU plus leucovorin. Raltitrexed was associated with less leucopenia, oral mucositis and stomatitis compared with 5-FU plus leucovorin. People receiving raltitrexed spent fewer days receiving chemotherapy and treatment for serious toxicity. Raltitrexed was also associated with increased anaemia and elevated liver transaminases that improved with continuing treatment. Two other trials (n=227 and n=495) found similar results.
Three other randomised trials (63, 38 and 61 evaluable patients) found that the most common grade 3 to 4 adverse effects from raltitrexed were diarrhoea, anaemia, elevation of liver enzymes ALT and AST, asthenia, and nausea or vomiting. A phase II study with 176 participants drew similar conclusions.