Patients with advanced colorectal cancer who received the FOLFOX4 regimen (fluorouracil [5-FU], leucovorin, oxaliplatin(Drug information on oxaliplatin) [Eloxatin]) responded significantly better to treatment, had fewer severe side effects, and lived months longer than did patients who received the standard IFL regimen (irinotecan [CPT-11, Camptosar] 5-FU, leucovorin), according to the initial results of a phase III trial presented at the 38th annual meeting of the American Society of Clinical Oncology.
Dr. Richard Goldberg, principal investigator for the trial and a medical oncologist at the Mayo Clinic in Rochester, Minn, said, "On our study, 71% of patients who received the FOLFOX regimen were alive 1 year after starting treatment, compared to 58% of patients who received the standard IFL therapy."
The trial, N9741, sponsored by the National Cancer Institute (NCI) and conducted by a network of researchers led by the North Central Cancer Treatment Group and the Mayo Clinic, compared three drug regimens: (1) the standard (control) IFL or Saltz regimen, (2) the FOLFOX4 regimen, and (3) irinotecan(Drug information on irinotecan) plus oxaliplatin.
FOLFOX4 Showed Early Promise
In a planned interim analysis of data from 795 patients who were enrolled between March 1999 and April 2001, researchers found that outcomes for patients receiving FOLFOX4 were significantly better than for those in the control arm. Patients in the FOLFOX4 arm lived about 4 months longer than did those in the IFL arm (median survival: 18.6 vs 14.1 months). They also had a significantly better time to tumor progression (median: 8.8 vs 6.9 months) and higher response rates (38% vs 29%). In addition, patients receiving FOLFOX4 experienced less toxicity, although many patients who take oxaliplatin develop a neurotoxicity that is unique to the drug.
Accrual to all arms of the trial except FOLFOX4 has been discontinued in light of the recent trial results. Patients already enrolled in one of the other two arms will be offered the option of switching to the FOLFOX4 arm in consultation with their physicians.
Investigators noted that the survival advantage for FOLFOX4 patients may, in part, be due to second-line therapies. Irinotecan is commercially available and was prescribed for 52% of patients after FOLFOX4 failed to further control disease; oxaliplatin, which at the time was not commercially available, was prescribed for only 17% of patients after IFL. These differences in second-line therapy may account for some part of the observed difference in survival.