COX-2 Inhibitor May Boost Capecitabine Response

July 2, 2002

HOUSTON-The COX-2 inhibitor celecoxib (Celebrex) appears to improve tumor response to capecitabine (Xeloda) and may help relieve hand-foot syndrome, according to results of a retrospective study by researchers at M.D. Anderson Cancer Center. Lead investigator Edward H. Lin, MD, assistant professor of medicine, Division of Gastrointestinal Medical Oncology, said that the group is planning a prospective trial of the combination.

HOUSTON—The COX-2 inhibitor celecoxib (Celebrex) appears to improve tumor response to capecitabine (Xeloda) and may help relieve hand-foot syndrome, according to results of a retrospective study by researchers at M.D. Anderson Cancer Center. Lead investigator Edward H. Lin, MD, assistant professor of medicine, Division of Gastrointestinal Medical Oncology, said that the group is planning a prospective trial of the combination.

Case-Control Study

The case-control study, reported in abstract form at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 2364), compared the results of 67 patients with metastatic colorectal cancer who were taking either capecitabine alone (1,000 to 1,250 mg/m² bid on days 1 to 14 of a 21-day cycle) or capecitabine plus celecoxib (200 mg bid for pain, started on day 1 and taken daily); the majority of patients in both groups were on the 1,000 mg/m² bid capecitabine dose.

Dr. Lin noted that patient demographics tended to favor the capecitabine-alone group. Their median age was lower than that of the combination group (55 vs 65, respectively), and more of the patients were chemotherapy naïve (31% vs 11%). The majority of patients in both groups had received one or two prior chemotherapy regimens. About half the patients in both groups had failed irinotecan (Camptosar) and/or oxaliplatin (Eloxatin, investigational in the United States).

Performance status, too, favored the capecitabine-alone group: No patients in the capecitabine-alone group were ECOG performance status 2, whereas 24% of the patients on the capecitabine/celecoxib combination were performance status 2.

Disease Stabilization

Despite the apparent demographic disadvantage, treatment results were better in the capecitabine/celecoxib group. "There seems to be improved disease stabilization among patients taking capecitabine and celecoxib as compared to capecitabine alone," Dr. Lin said. "And the stable disease has lasted longer than 3 months."

Among patients taking the capecitabine/celecoxib combination, 62.5% achieved stable disease, compared with 22.8% of patients taking capecitabine alone. Partial responses were seen in four patients taking the combination (two of whom had taken irinotecan) and in three patients on the single-agent therapy (all of whom were chemotherapy naïve).

Median time to progression was 6 months on the combination therapy, compared with 3 months in the single-agent group.

An early objective of the study was to evaluate celecoxib’s effect on hand-foot syndrome. Dr. Lin noted that both diarrhea and hand-foot syndrome were noticeably reduced in patients taking the capecitabine/celecoxib combination (see table).

The incidence of grade 2-3 diarrhea was twice as high in the capecitabine-alone group as in the combination group (28.6% vs 15.6%, respectively), and grade 2-3 hand-foot syndrome was three times more common (34.3% vs 12.5%). Dr. Lin noted that only one patient in the group receiving celecoxib had grade 3 hand-foot syndrome.

Dr. Lin suggested that the celecoxib should be continued through the 1-week capecitabine rest period because stopping the drug during this time appears to compromise its hand-foot syndrome benefits. Anecdotal evidence from patients who stopped celecoxib altogether because of cost and lack of insurance coverage indicates that hand-foot syndrome may return when the drug is discontinued.

A recent, unpublished finding, Dr. Lin said, is that five M.D. Anderson patients who developed severe hand-foot syndrome on capecitabine alone experienced complete resolution of the problem shortly after starting on celecoxib.