Where do you see these new agents taking prostate cancer treatment?

Dr. Crawford: I think we’re going to see several important things happen. One, there’s going to be a shift toward using a number of these drugs earlier in the disease process, prior to chemotherapy. For example, an exciting drug waiting in the wings is radium-223, which is Alpharadin [a bone-seeking radionuclide from Algeta and Bayer]. It just had a positive trial, so I think we’re going to see that integrated earlier.

In just about every cancer we cure, it’s not monotherapy that works; it’s multidrug therapy. I’ve been around long enough to remember when platinum came out and everybody was excited about monotherapy in testes cancer. You know what? It got responses but it didn’t cure as many people as you cure when you start putting drugs together, like three drugs. If you look at lymphomas and leukemias, it’s not monotherapy; it’s multiple attacks.

So now we’ve got a lot of arrows in our quiver for prostate cancer, which excites me. And we’ve got to start thinking about which patient we’ll put with which agent, and not just think about monotherapy, but about sequencing one drug after the other—mounting an attack. I can see using sipuleucel-T, which interferes with the production of testosterone from multiple sources, with MDV3100, which is a super anti-androgen, to really super-deprive the cancer of androgen.

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I can see in a few years, in patients who are progressing, that it could be a combination of, perhaps, sipuleucel-T and abiraterone, and maybe MDV3100 and chemo or radium. You have to figure out if it’s better to do it that way than to sequence them. Those are the kinds of things you have to start thinking about.

We’ll see a synergism, and we may turn advanced prostate cancer into a chronic disease.

Prostate cancer already is often considered a chronic disease. What would change?

Dr. Crawford: There are 240,000 men diagnosed every year, and 30,000 die, so a lot more people are diagnosed than die of the disease. A lot of people have prostate cancer and they die with it, rather than of it, and that’s like a chronic disease. So what we have here is a lot of overtreatment to a degree, and that’s what all the controversy is about—early screening, diagnosis, and treatment. As a matter of fact, I’m one of the investigators on the PLCO [Prostate, Lung, Colorectal, and Ovarian Cancer] Screening Trial.

But we’re talking about a subset of patients here that contribute to the 30,000 men who die every year of the disease. We’re talking about making prostate cancer a chronic disease for even the most advanced cases.

We’ve got the tools now; we’ve just got to be smart enough to use them and aggressive enough to deal with this disease.

Editor’s note: Dr. Crawford is an advisory board member for Amgen, Dendreon, Janssen, and sanofi-aventis as well as for Ferring Pharmaceuticals, where his wife is an employee. His coauthor on the Oncology review, Dr. Flaig, is a consultant to sanofi-aventis and has received an honorarium from Amgen.