NANTES, France—European researchers are moving beyond colorectal cancer regimens based on infusional fluorouracil(Drug information on fluorouracil) (5-FU) to comparing combinations and to examining the effects of scheduling on response and time to progression, according to Jean-Yves Douillard, MD, PhD. Professor Douillard, who developed a widely-used regimen for colorectal cancer, is professor of medical oncology and head of the department of medical oncology, Centre Rene Gauducheau, at the University of Nantes in France.
European clinicians view the value of chemotherapy for colorectal cancer as well established and favor infusional over bolus 5-FU, according to Professor Douillard. "A combination of fluorouracil, leucovorin, and irinotecan(Drug information on irinotecan) (CPT-11, Camptosar) or oxaliplatin(Drug information on oxaliplatin) (Eloxatin) is now becoming standard therapy," he said. "Most use a simplified de Gramont regimen, with a 5-FU bolus of 400 mg/m2 followed by 5-FU at 2.4 to 3.6 g/m2 over 46 hours, repeating every 2 weeks" (see Table 1).
Ongoing European studies in advanced colorectal cancer include comparisons between single agent 5-FU/leucovorin and various combinations and comparisons of combinations. European researchers are also experimenting with variations in drug scheduling, either in exclusive chemotherapy or in combination with surgery for resectable patients.
Ongoing Trials Summarized
Professor Douillard summarized these ongoing trials.
A German trial is comparing the German AIO regimen (2,600 mg/m2 5-FU given as a 24-hour infusion plus 500 mg/m2 leucovorin weekly x 6 with 1 week rest, continuing for 18 weeks to the same regimen plus irinotecan at 80 mg/m2/week, but with the 5-FU dose reduced to 2,000 mg/m2. Preliminary results of this 430-patient trial, which were presented at the 2002 American Society of Clinical Oncology meeting (Kohne et al, ASCO abstract 532) showed a median progression-free survival of 8.5 months for the irinotecan arm vs 6.5 months for the 5-FU/leucovorin arm (P < .0001). "This is one of the longest time to progression periods reported so far in this population of patients," Professor Douillard said.
An ongoing UK study (FOCUS) in 2,100 patients is comparing five regimens:
