With newer agents for advanced prostate cancer, how has your approach changed?

Dr. Lowentritt“My approach is to get patients the most complete treatment at the earliest appropriate time. Specifically, we’re talking about castrate-resistant prostate cancer and metastatic cancer, which almost needs to be considered a different disease because we think of prostate cancer as a slow-growing and slowly progressing disease. Once you have a castrate-resistant metastatic prostate cancer, these are the patients who are likely going to die of cancer.

In general, we try to treat with immunotherapy (Provenge) then continue close monitoring and moving on to other hormone manipulation medications like Zytiga and Xtandi.

Medicines like Zytiga work across the whole body on a hormone-synthesis level to prevent testosterone from being made pretty much anywhere. We know prostate cancer cells throughout the body can make low levels of testosterone and that can feed back to the cancer, so the cancer can become somewhat self-sustaining.

Anti-androgens block the ability of testosterone to bind at a cell level so they accomplish similar things, but right now Zytiga-type medications are approved by the FDA for use at an earlier stage.

Technically, we are only supposed to give Xtandi after chemotherapy. As a general trend, we see chemotherapy pushed further back in the treatment line because we have more specific prostate cancer treatments and the ability of either immunotherapy or advanced hormone therapy or hormone manipulation to stop the cancer.”

Benjamin Lowentritt, MD

Baltimore

“I’m employed in an integrated system, working alongside medical oncologists. So it’s not necessarily an advantage to the patient, or for me, to hold on to advanced cancer patients and manage their chemotherapy. While it’s totally appropriate for urologists to do that, in our system, it benefits everybody for advanced cancer patients to move to the oncologist when they fail hormonal therapy.

Our group does all go to the meetings, come back, read the literature, and come to a consensus. When I send patients out, generally they will get Provenge. Those who are minimally symptomatic will likely start Zytiga. Those who are failing Provenge and Zytiga go on to get Taxotere. It may look different next year, but in 2013, that is the sequence that makes the most sense.

Provenge has shown that it has a survival benefit, although it doesn’t have a PSA response. If a patient with a rising PSA is put on Provenge and the PSA keeps going up, it can be very uncomfortable. Generally, we give Provenge but then pretty quickly move to something else because we want patients to at least feel like they are being treated by getting their PSA back down.

Everything fails in this patient, but we’ve gotten very good responses initially-with advanced hormonal therapy and more of a complete androgen blockade that’s even stronger than Lupron.”

Brian Link, MD

Oklahoma City

“I’ve been around a long time, so I’ve seen a lot of approaches. I started when they still used estrogen for treatment of aggressive cancers. Now, when the cancer goes beyond the capsule, I try LHRH analogs, and usually the majority will respond. I have had a few patients present with PSAs in the thousands and it does go down, just to show you that the PSA is still worthwhile.

If patients want to be more aggressive, I give them something like Casodex, which is an anti-androgen. Again, old school but it does work.

In patients on LHRH and resistant to measures to this point, there are agents such as Zytiga, which we’ve had a little experience with and that hasn’t been terribly positive. The majority of patients who had to go on those drugs ended up dying. It may have given them a few months but it’s not a complete reversal.

I’ve been really impressed with LHRH agonists; they work very well. We use it as part of the radiation therapy. If that fails, we use it independent of the radiation.

LHRH basically works at one level while anti-androgens affect the same thing but work at another level. LHRH has basically been shown to be more effective with fewer side effects.”

Irving Fishman, MD

Houston

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