SILVER SPRING, Maryland—Due to concerns about the postmarketing safety of the bolus or Saltz regimen of Camptosar (irinotecan, Pharmacia) combined with fluorouracil(Drug information on 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 drugs—the 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 arms—oxaliplatin/5-FU/leucovorin and irinotecan(Drug information on irinotecan)/oxaliplatin.
Assessing Mortality
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.
