My Most Difficult Choice

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Scientists initially became interested in the COX-2 enzyme because it's found in so many cancer cells. When active, COX-2 produces a chemical called a prostaglandin that helps keep the stomach lining healthy. It also helps the kidney and blood platelets function properly. In tumors, however, prostaglandin becomes a bad actor, an evil conspirator that helps build the new blood supplies that tumors need to grow. COX-2 also makes cancer cells more resistant to the body's immune response and more resistant to drugs. What would happen, scientists wondered, if you suppressed the COX-2 enzyme with an inhibitor such as Celebrex? "It makes sense that if you shut off the prostaglandin by turning off the COX-2, then the other things wouldn't happen," says Altorki. "The science is so strong, so persuasive."

And still unproven beyond the lab. Altorki and Keresztes had to halt my study when the Vioxx news broke. When they decided to resume, patients like me had to decide whether to continue and risk heart attack or stroke down the road. The doctors no longer require new subjects to enroll for a full two years, to track long-term survival--the heart danger seemed to kick in after about 18 months--but they are offering it as an option. Anyone who re-upped had to sign a revised waiver specifically advising them of the possible increased risk. On paper that risk wasn't much. In one study, and one study only, 2 out of 100 Vioxx users had cardiovascular incidents. The placebo group had 1 in 100. So the risk doubled. That's the headline (it's certainly the one I'd write). But if you read beyond the headline, the underlying risk is pretty low. It's important to note that there's no actual proof that Vioxx alone increases heart risk.

Here's what led me back to the trial: first, I didn't want to lose the potential benefit. Second, I'm middle aged and in pretty good shape, and thus younger and fitter than most people with my flavor of cancer. I figured the slightly elevated heart risk was, for me, a more manageable proposition. That's pure rationalization, of course. The bonus round: for an aging gym rat, Celebrex is a wonder at relieving the aches and pains that come from too much exercise.

There's another, more important part of the equation. The worst side effect of cancer that I can think of is being dead. The cure rate for all lung cancer patients is 14%; it's even lower for esophageal cancer. Hell, the treatment alone can kill you, given the toxicity of cancer drugs. "You tell me, what risk are these people willing to take?" asks Altorki. Only so much, it seems; about half of the surviving subjects in my study opted out.

COX-2's prospects as a cancer fighter continue to intrigue scientists. "Clinically, we are still at the beginning," says Dr. Steven Dubinett, director of the thoracic oncology program at UCLA Medical School. "It would really be a travesty if we were unable to continue." Dubinett says about 10% of his studies' participants dropped out. He is investigating whether Celebrex can prevent cancer, but he faces a real dilemma: How can he give to otherwise healthy people a drug that might not work and might increase their risk of heart attack? "It's going to make it very difficult to do long-term-treatment projects," says Keresztes. Dubinett's approach is to recruit ex-smokers, people who have already substantially increased their risk of both lung cancer and heart attack. Pick your poison.