They evaluated the regimen effects on survival, symptom palliation, and quality of life.
Some 905 patients were included in the study and were randomly assigned to 1 of 3 treatment regimens.
The de Gramont regimen (n = 303) comprised of folinic acid 200 mg/m2, fluorouracil bolus 400 mg/m2, and infusion 600 mg/m2 on days 1 and 2, repeated every 14 days.
The Lokich regimen (n = 301) consisted of protracted venous infusion of fluorouracil 300 mg/m2 daily.
The third regimen (n = 301) was raltitrexed 3 mg/m2 given intravenously every 21 days.
Median follow-up of survivors was 67 weeks.
| Raltitrexed was more toxic and resulted in inferior quality of life than other regimens.
For the de Gramont, Lokich, and raltitrexed groups, median survival was 294, 302, and 266 days, respectively.
The hazard ratios for overall survival were 0·88 for de Gramont versus Lokich, and 0·99 for de Gramont versus raltitrexed.
The team observed an increase in treatment-related deaths on raltitrexed (de Gramont 1, Lokich 2, raltitrexed 18) due to combined gastrointestinal and hematological toxicity.
Furthermore, patients' assessment of quality of life showed that raltitrexed was inferior to the fluorouracil-based regimens, especially in terms of palliation and functioning.
Professor T. S. Maughan, of the Velindre Hospital, Cardiff, Wales, said on behalf of fellow authors, "The deGramont and Lokich regimens were similar in terms of survival, quality of life, and response rates.
"However, the Lokich regimen was associated with more central line complications and hand-foot syndrome."
"Raltitrexed showed similar response rates and overall survival to the de Gramont regimen and was easier to administer, but resulted in greater toxicity and inferior quality of life," it was concluded.