Aspirin, COX-2 Inhibitors Effective as Adjuvant Therapy in Stage III Colon Cancer

Larry Schuster

May 16, 2005

May 16, 2005 (Orlando) — Patients with stage III colon cancer may benefit from aspirin as much as from surgery and standard chemotherapy alone. A preliminary study found aspirin contributed to an additional 50% reduction in risk of recurrence and death when used as adjuvant therapy in these patients.

The prospective nonrandomized study of 830 patients, lead by researchers at Dana-Farber Cancer Institute, also found a similar result for celecoxib (Celebrex) and rofecoxib (Vioxx). Charles Fuchs, MD, MPH, associate professor of medicine, at Dana-Farber, presented the results here at the American Society of Clinical Oncology 2005 annual meeting.

In Dr. Fuchs's report, he said after a median follow-up of 2.4 years, the risk or recurrence of colon cancer was 55% lower and the risk of death was 48% lower among regular aspirin users compared with nonusers. Patients who used celecoxib or rofecoxib had a 44% reduced risk of recurrence.

Of the 830 patients studied, 8.7% used aspirin, and most of them used 325 mg per day or every other day, while 4.3% of patients reported regular use of one of the other two drugs. The patients began taking aspirin during the start of chemotherapy and continued throughout the study.

All patients received the standard chemotherapy and surgery. The chemotherapy provides about 35% improvement in survival compared with surgery alone for that stage of colon cancer, Dr. Fuchs said in an interview. In comparison, aspirin or the two cyclooxygenase 2 (COX-2) inhibitors produced a reduction in risk of recurrence and death that was about 50% beyond what was achieved by chemotherapy after surgery.

"These data would suggest that the benefit observed is at least as comparable as any cancer therapies we are using now," Dr. Fuchs told Medscape. He noted, however, that the therapies in use have been in randomized trials, whereas this preliminary study was not randomized.

Meantime, Dr. Fuchs advises against using aspirin as an adjuvant therapy until the results can be confirmed in rigorous trials. Among his own patients, Dr. Fuchs advises using aspirin as preventive therapy to reduce the risk of developing subsequent polyps and new cancers.

That recommendation is based on convincing evidence in previous studies showing that aspirin could reduce the risk of cancer. Based on these studies, Dr. Fuchs wanted to test out the hypothesis that if aspirin could prevent onset of cancer, maybe it could also be used in an adjuvant setting. In addition, Dr. Fuchs chose to use the two COX-2 inhibitors to test whether the effect could be associated with the COX-2 target. As a result, the study does provide evidence that COX-2 indeed plays an important role in cancer and cancer suppression. Despite the positive outcome of this aspirin trial, though, so far, there are no plans for a phase 3 trial.

Dr. Fuchs is the principal investigator for a randomized stage IV colon cancer trial (BICC-C) that will compare chemotherapy plus placebo vs chemotherapy plus celecoxib. Results are anticipated for next year. BICC-C is a phase 3, metastatic colorectal cancer trial sponsored by Pfizer Inc.

Randall Harris, MD, PhD, told Medscape that the study results were "very impressive, very interesting, and very consistent with chemoprevention trials using aspirin and other compounds that block COX-2." Dr. Harris is a member of the Ohio State University Comprehensive Cancer Center in Columbus and was the editor of the book COX-2 Blockade in Cancer Prevention and Therapy.

"This sounds as if it's one of the early studies of NSAIDs [nonsteroidal anti-inflammatory drugs] and selected COX-2 blockers showing they could have important effects in the treatment of colon cancer," Dr. Harris said. It also suggests that doses of the drug that are subtherapeutic for arthritis appear to be highly therapeutic in cancer. "These available data suggest low doses are effective."

"We think these compounds interfere with COX-2 and other targets or other mechanisms, involved with colon cancer," Dr. Harris said. They appear to help reestablish apoptosis among cancer cells and seem to block angiogenesis."

"I would strongly support further study of selective and nonselective COX-2 inhibitors to determine dose, duration, adverse effects, and cost-effectiveness as adjuvant therapy against colon cancer and other types of malignancies, particularly breast, prostate, and lung, since these have been shown to respond to NSAIDs in cancer prevention studies.

"We should move quickly to evaluate these compounds, which should not have the adverse effects of chemotherapeutic drugs," Dr. Harris said.

ASCO 2005 annual meeting: Abstract 3530. Presented May 16, 2005.

Reviewed by Gary D. Vogin, MD

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