Patients with advanced
colorectal cancer who received the FOLFOX4 regimen (fluorouracil [5-FU],
leucovorin, 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
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 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.