With newer agents such as oxaliplatin and irinotecan being used as first line therapy for advanced CRC, raltitrexed's place in therapy is limited and should only be used in a select group of patients. It may be a used as an alternative for fluorouracil or capecitabine in patients who are unable to tolerate these drugs. Raltitrexed is currently not approved in the United States and is recommended only in clinical trials in the United Kingdom.r
Four large phase III trials have been conducted comparing raltitrexed with fluorouracil/folinic acid (5FU/FA) in advanced colorectal cancer.r, r, r, r Three of the four trials compared raltitrexed with bolus 5FU/FA (Mayo) regimen and one trial compared raltitrexed with bolus and infusional 5FU/FA (De Gramont) regimen.
The trials were well balanced in both treatment arms and end points included overall survival, progression-free survival, response rates and toxicity.
Efficacy
Overall, median survival and response rates of raltitrexed were comparable to 5FU/FA. However, in two of the four trials, time to progression was significantly shorter in the raltitrexed arm.r,r
Efficacy |
Cunninghamr |
Maughanr |
Cocconir |
Pazdurr |
|
Raltitrexed |
5FU/FA |
Raltitrexed |
5FU/FA |
Raltitrexed |
5FU/FA |
Raltitrexed |
5FU/FA* |
Median Survival (months) |
10.3 |
10.3 |
8.8 |
9.8 |
10.9 |
12.3 |
9.7 |
12.7 |
Median PFS (months) |
4.7 |
3.6 |
4.8 |
5.7 |
3.9 |
6.0 |
3.1 |
5.6 |
Response rates (%) |
19.3 |
16.7 |
18 |
23 |
19 |
18 |
14.3 |
15.2 |
* De Gramont regimen
Toxicity
When compared with bolus 5FU/FA regimens, raltitrexed had a significantly lower incidence of both severe leucopenia and mucositis.r However, when compared to the infusional 5FU/FA De Gramont regimen, raltitrexed was associated with greater toxicity and treatment related deaths (18 versus 1). 3 of the deaths were in patients who did not have appropriate dose adjustments for diarrhoea or thrombocytopenia.r
Toxicityr
© Annals of Oncology 1996
Toxicityr
© Lancet 2002