Celecoxib Shows Promise Against Recurrent Prostate Cancer

Alicia Ault

October 12, 2004

Oct. 12, 2004 (New Orleans) — The cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) effectively held prostate-specific antigen (PSA) levels in check in an early study of men with recurrent prostate cancer, according to researchers here at the American College of Surgeons 90th annual clinical congress.

In the study, 40 men who had rising PSA levels after radical prostatectomy or external beam radiation therapy were given 400 mg of celecoxib twice daily for at least one year. PSA levels were measured at three, six, and 12 months after treatment began. The impact was evaluated by calculating PSA doubling times and the slope of the PSA change before and after treatment.

At one year, PSA levels for 35 of the 40 men were measured (the five remaining men had not yet reached a year of treatment). Of the 35, five men had stable or decreased PSA levels and of the remaining 30, two had disease progression, said Raj Pruthi, MD, from the Division of Urologic Surgery at the University of North Carolina in Chapel Hill, in a presentation to reporters. Also of the remaining 30, 22 men had a doubling in PSA levels that took longer than one year, seven had a doubling within six to 12 months, and one man had a doubling in PSA levels in less than six months.

In some patients, there was a prolonged plateauing or decrease in PSA out to 18 months, Dr. Pruthi said. But a few patients also showed signs of resistance to therapy, and those patients seemed to have the most aggressive disease.

Dr. Pruthi characterized the study as "very early" — essentially, initial proof of concept that COX-2 inhibitors like celecoxib might be useful in prostate cancer. "This is literally the first step," he told Medscape in an interview, noting that the literature supported the notion that COX-2 inhibition might have antitumor and anti-angiogenic effects.

Patients are being closely monitored for known nonsteroidal anti-inflammatory drug adverse effects; so far, there has been no sign of gastrointestinal or renal toxicity. They are also being watched for cardiovascular effects, said Dr. Pruthi, although he added that in many published studies, celecoxib has been shown to have no increased incidence of heart attack or stroke, unlike Merck's recently withdrawn COX-2 inhibitor rofecoxib (Vioxx).

But Dr. Pruthi said he did not consider the questions about cardiovascular adverse effects to be settled. "These are important issues for investigators and cardiologists to figure out," he said.

Even so, he considers celecoxib much safer to give his prostate cancer patients than the alternative hormonal therapies or chemotherapies. "There's nothing else I can offer my prostate cancer patients that even approaches that level of safety," Dr. Pruthi told Medscape.

He and his colleagues are now moving on to further phase II trials in patients with different stages of prostate cancer, and they have also begun a trial in bladder cancer.

Dr. Pruthi predicted that even with this early data and questions about cardiac effects, COX-2 inhibitors will begin to see wider use in cancer through off-label prescribing by oncologists. "There's no question there will be off-label use [of COX-2 inhibitors] in prostate cancer," he said, noting that he had begun to prescribe them for some of his patients.

The study was investigator-initiated, but Pfizer, the maker of Celebrex, provided the study drug, said Dr. Pruthi.

ACS 90th Annual Clinical Congress: Abstract S100. Presented Oct. 11, 2004.

J Am Coll Surg. 2004;199(3 suppl):S100. Presented Oct. 11, 2004.

Reviewed by Gary D. Vogin, MD

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