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COX-2 Inhibitors Decrease Toxicity due to Chemotherapy; May Help Arrest Tumor Progression

COX-2 Inhibitors Decrease Toxicity due to Chemotherapy; May Help Arrest Tumor Progression

HOUSTON—Inflammation is a common link between the toxicity of chemotherapy
and cancer progression, and the possibility that anti-inflammatory treatments
might help both is attracting more research attention. "Cancer is a nonhealing
wound with persistent inflammation," Edward H. Lin, MD, said, quoting Harold
Dvorak, MD, of Beth Israel Hospital in Boston. Dr. Lin is assistant professor
of gastrointestinal medical oncology at the University of Texas M.D. Anderson
Cancer Center in Houston.

"Pro-inflammatory factors in a wound are very similar to what cancer
utilizes as a growth medium," Dr. Lin added. Furthermore, COX-2 is involved at
every stage of carcinogenesis from hyperplasia to metastasis. COX-2 promotes
tumor angiogenesis, induces tumor cell growth, and inhibits apoptosis.

In general, patients on capecitabine (Xeloda) have significantly less
diarrhea, stomatitis, nausea, and alopecia than patients receiving fluorouracil
(5-FU), but significantly more hand-foot syndrome (HFS), Dr. Lin noted. The
manifestations of HFS are the classic signs associated with inflammation: rubor,
turgor, calor, and dolor (redness, swelling, heat, and pain). This suggested to
Dr. Lin and colleagues at M.D. Anderson Cancer Center that inhibiting COX-2,
which is preferentially associated with inflammation, might have therapeutic
benefits.

HFS Significantly Reduced

Dr. Lin reviewed records of patients at M.D. Anderson Cancer Center who had
taken capecitabine with (n = 32) or without (n = 35) celecoxib (Celebrex) at
200 mg po bid for metastatic colorectal cancer. In data from the case-control
study previously presented at the American Society of Clinical Oncology
meeting, Dr. Lin found that adding celecoxib decreased the incidence of grade 2
or worse HFS from 34.5% to 12.5% (P = .037) and the incidence of grade 3
or worse diarrhea from 28.6% to 3.1% (P = .005). Median time to
progression in a group of patients that had been pretreated with 1 to 3
different chemotherapy regimens increased from 3 months to 6 months (P =
.002).

"Patients taking capecitabine for more than 6 months often develop fibrotic
changes on the hands and feet," Dr. Lin said. "Adding celecoxib seemed to be
able to prevent chronic HFS, with immediate pain relief and subsequent return
of normal skin. We are currently collecting a group of patients who have
developed HFS on capecitabine and will treat them with celecoxib."

New Data on Survival

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