HOUSTONInflammation 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(Drug information on capecitabine) (Xeloda) have significantly less diarrhea, stomatitis, nausea, and alopecia than patients receiving fluorouracil(Drug information on 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(Drug information on 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