SILVER SPRING, MarylandDue to concerns about the postmarketing
safety of the bolus or Saltz regimen of Camptosar (irinotecan, Pharmacia)
combined with fluorouracil (5-FU) and leucovorin (IFL) as a first-line
treatment for metastatic colorectal cancer, the Food and Drug Administration
asked its Oncologic Drugs Advisory Committee (ODAC) to review the issue.
By a 15 to 0 vote, ODAC members reaffirmed the safety of the combination
treatment and rejected the idea that FDA remove its use from the agency’s
approved labeling for Camptosar.
ODAC members also unanimously rejected changing the starting dose for bolus
IFL injections, but did support making some modification to the Camptosar
label. After some discussion, the committee generally suggested that the FDA
and Pharmacia work out the exact wording changes.
The FDA approved the IFL combination in April 2000 for first-line use in
metastatic colorectal cancer and listed two regimens for delivering the drugsthe
bolus injection and a slower infusion method known as the Douillard regimen.
The agency’s concern was stimulated by an analysis of a North Central
Cancer Treatment Group (NCCTG) trial (N9741) that, using a new approach to
assess mortality, showed an increase in deaths among patients who received IFL
bolus injections. This study, which involved 841
colorectal cancer patients, used the IFL bolus regimen as the control against
two other armsoxaliplatin/5-FU/leucovorin and irinotecan/oxaliplatin.
Instead of assessing mortality by the usual 30 days from last treatment,
Study N9741 used 60 days from start of therapy. According to an FDA analysis of
the study data, the results showed that deaths from all causes were 4.8% for
the IFL bolus regimen vs 1.8% in each of the two experimental arms.