Celebrex Bests Vioxx as Potential Cancer Fighter

Despite cardiovascular risks, painkiller appears to block key protein for cancer cell replication

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HealthDay Reporter

TUESDAY, March 1, 2005 (HealthDayNews) -- Celebrex, one of the cox-2 painkillers under fire for increasing heart attack and stroke risk, may actually slow certain cancers in a way that its cousin, Vioxx, does not, according to new preliminary research.

Both drugs, known as cox-2 inhibitors, have already been shown to inhibit the growth of tumors that depend on the cox-2 enzyme, as happens with some prostate and breast cancers.

But a new study finds that Celebrex (celecoxib) appears to fight prostate cancer on another front, by blocking a key protein that is essential to the replication of cancer cells. This latest report appears in the March 1 issue of Clinical Cancer Research.

"Celecoxib can mediate anti-tumor effects by mechanisms in addition to targeting cox-2, which is its known target," said lead researcher Dr. Andrew Dannenberg, director of cancer prevention at the Weill Medical College of Cornell University in New York City. "This suggests that the agent's overall anticancer activity may reflect cox-2 inhibition and other properties."

In their study, Dannenberg's team treated human prostate cancer cells that did not have the cox-2 enzyme with Celebrex. The researchers found that cells treated with the drug did not reproduce as quickly as similar untreated cells. Further research determined that Celebrex was blocking cyclin D1.

"We were able to demonstrate that at clinically achievable concentrations of the drug in cells that don't express cox-2, the drug still has activity," Dannenberg said. "Based on these results, it's conceivable it will have effects in human tumors that do or do not express cox-2," he added.

However, when the researchers tried the same experiment using Vioxx, they found the cancer cells continued to reproduce.

"This makes the point that all cox-2 inhibitors are not created equal," Dannenberg said.

They were, however, given equal treatment two weeks ago, when a U.S. Food and Drug Administration advisory panel voted to recommend that Celebrex, Vioxx and Bextra stay on the market, while acknowledging the cardiovascular dangers of the drugs.

On Tuesday, the Louisiana health department announced it will impose additional safeguards, which will go into effect on March 15. Those safeguards will require doctors to supply a diagnosis code for every prescription for both Celebrex and Bextra, telling the pharmacist why the patient needs the medication.

Vioxx is not affected because it was removed from pharmacy shelves last fall by its manufacturer after trials revealed the heart risks.

Despite the concerns about the cardiac risk of cox-2 inhibitors, Dannenberg believes that when it comes to cancer, the considerations of these drugs' ability to fight tumors should be the first priority.

"Cox-2 inhibitors have been shown to have a small increase in risk of cardiovascular complications when taken long term," Dannenberg noted. "However, it is extremely important in the oncology world to recognize that efficacy is of greater concern. This new study makes the observation that celecoxib can act by more than a single mechanism to inhibit tumor growth."

Dannenberg noted that his work is not a clinical study, and that the use of Celebrex in fighting cancer needs to wait for the outcome of several ongoing clinical trials.

"Decision-making on clinical use should be based on the results of these clinical trials," he said.

Another expert thinks that much more needs to be done before Celebrex can find a role in fighting cancer.

"It is surprising to me that the authors did not try to see what would happen to these cells when treated with aspirin or one of the inhibitors which block cox-1 specifically, since these cells did express cox-1," said Dr. Raymond N. DuBois, the director of the Vanderbilt-Ingram Comprehensive Cancer Center at Vanderbilt University.

"We have found that some ovarian cancer cells are very dependent on cox-1 expression, and respond very well to cox-1 inhibitors," DuBois added.

DuBois noted that in the study, higher doses of Celebrex seemed to be more effective.

"Unfortunately, these higher doses in humans seem to be associated with adverse cardiovascular effects," he added. "Thus, these selective inhibitors may have some role in treatment of prostate cancer, but their long-term use for prevention at these higher doses may not be well-tolerated."

One heart expert said he thought that the use of cox-2 inhibitors to fight cancer was a tricky matter.

"We currently do use many drugs for cancer treatment that are themselves toxic to the heart," said Dr. Scott D. Solomon, director of noninvasive cardiology at Brigham and Women's Hospital, in Boston. "Ultimately, I believe we will need large clinical trials to sort this out, with longer follow-up times, since a large enough trial should provide the 'net' between efficacy and safety."

Moreover, Solomon is concerned with the ultimate benefit to patients.

"Another thing to remember, though, is whether a reduction in cancer cell proliferation as suggested here will result in net benefit to the patient, such as longer life," he said. "This will be necessary to offset any potential increased cardiovascular risk. In short, this is simply more information to fill out our current knowledge of the possible benefits of cox-2 inhibitors."

More information

The American Cancer Society can tell you more about new cancer treatments.

SOURCES: Andrew Dannenberg, M.D., director, cancer prevention, Weill Medical College of Cornell University, New York City; Raymond N. DuBois, M.D., Ph.D., director, Vanderbilt-Ingram Comprehensive Cancer Center, B.F. Byrd Jr., professor, molecular oncology, medicine, cancer biology and cell-developmental biology, Vanderbilt University Medical Center, Nashville, Tenn.; Scott D. Solomon, M.D., director, noninvasive cardiology, Brigham and Women's Hospital, and associate professor, medicine, Harvard Medical School, Boston; March 1, 2005, Clinical Cancer Research

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