PORTLAND, OregonIn a phase II trial of patients with unresectable or
metastatic colorectal cancer, celecoxib (Celebrex) given with irinotecan
(CPT-11, Camptosar), fluorouracil (5-FU), and leucovorin (IFL) appears to
reduce toxicity, Charles D. Blanke, MD, associate professor of medicine,
Oregon Health & Science University, said at the 38th Annual Meeting of
the American Society of Clinical Oncology (abstract 505).
"Preliminary data suggest that celecoxib may be important in the IFL
profile," Dr. Blanke said.
IFL is the standard of care for these patients, but the weekly schedule
is associated with severe neutropenia and grade 3-4 diarrhea. The objective
response rate with the weekly schedule is 39%, median progression-free
survival 7 months, and median overall survival 14.8 months.
Cyclooxygenase-II (COX-2) is expressed in most colorectal cancers, and
expression is correlated with larger tumor size, deeper invasion, and higher
rates of lymph node involvement and distant metastasis. "In potentially
curatively resected patients, a high level of COX-2 expression in the
primary tumor correlates with a statistically shorter disease-free
survival," Dr. Blanke said.
There are a number of mechanisms by which COX-2 expression is linked to
the initiation or promotion of invasive cancer, he said, including
angiogenesis; increased tumor cell proliferation, motility, and general
ness; and induction or resistance to apoptosis.
Celecoxib is FDA approved for treatment of arthritis and familial
adenomatous polyposis (FAP). For FAP, the approved dose is 400 mg twice
daily. In preclinical studies, celecoxib has been combined with
chemotherapeutic agents, such as 5-FU and irinotecan. Rodent studies suggest
that celecoxib may be associated with decreased diarrhea when given with
Phase II Trial