BOSTONIn a letter to the editors of the New England
Journal of Medicine, researchers from two cooperative groups call for
"vigilant monitoring" of patients receiving the combination of
irinotecan (Camptosar), fluorouracil (5-FU), and leucovorin for metastatic
colorectal cancer, due to an excess number of deaths observed in patients
receiving this combination in two randomized NCI-sponsored trials. They added
that specific clinical factors that increase the risk of adverse effects in
patients receiving this regimen have not yet been identified.
The Journal released the letter on May 17, 2001, a month
before its publication date of June 21, 2001, due to its "potential
importance in the treatment of colorectal cancer."
Last year, Saltz et al reported the superiority of the
irinotecan/5-FU/leucovorin combination over irinotecan alone or 5-FU/leucovorin
in the initial treatment of metastatic colorectal cancer (N Engl J Med
343:905-914, 2000). The FDA subsequently approved the treatment, and many
oncologists consider it the standard of care.
Now, researchers conducting North Central Cancer Treatment
Group (NCCTG) trial N9741 and Cancer and Leukemia Group B (CALBG) trial C89803
report "an imbalance in the number of deaths occurring within 60 days
after the initiation of treatment."
In N9741, which involves patients with advanced disease, there
have been 14 deaths in the irinotecan/5-FU/leucovorin arm, compared with 5 each
in the oxaliplatin/5-FU/leucovorin arm and the oxaliplatin/irinotecan arm. In
the second study, a surgical adjuvant trial, there have been 14 deaths among
patients receiving the Saltz combination vs 5 in patients taking
5-FU/leucovorin. The investigators report that on the basis of these data, the
data and safety monitoring boards of both trials recommended that enrollments
in the studies be suspended.
The letter’s authorsDaniel Sargent, PhD, and Michael O’Connell,
MD, Mayo Clinic; Donna Niedzwiecki, PhD, Duke University; and Richard Schilsky,
MD, Chicagostate that the Saltz regimen "should continue to be an
option in this treatment setting, but in our experience has been associated
with an excessive rate of early deaths." They suggest as an alternative
the FDA-approved infusion schedule reported by Douillard et al (Lancet
355:372, 2000) and given in the irinotecan package insert.