PORTLAND, OregonIn a phase II trial of patients with unresectable or metastatic colorectal cancer, celecoxib(Drug information on celecoxib) (Celebrex) given with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), fluorouracil(Drug information on 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 irinotecan.
Phase II Trial