What's New in the Treatment of Prostate Cancer?

Treatment for metastatic castrate resistant prostate cancer

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Many things have changed in the treatment of prostate cancer over the last several years. This is especially true in the treatment of metastatic castration-resistant prostate cancer (mCRPC). This is prostate cancer that has failed a primary treatment (surgery, radiation etc.) and has gone on to fail hormonal treatment (androgen blockade or castration). This also applies to patients who present with metastatic disease and have failed hormonal treatment.

Prior to the onset of use of chemotherapy for these patients the average life span was about 8 months. Chemotherapy improved on this but is not curative. 

Since 2010 several new treatments have become available for patients with mCRPC. The following is a brief description of the newest treatments.

  1. Abiraterone Acetate (Zytiga) – Zytiga inhibits the production of testosterone precursors and decreases the levels of testosterone. It is usually given with prednisone. Zytiga was originally indicated in patients who had failed docetaxel (chemotherapy) but more recent studies have shown benefit in the pre-chemo patient. One study showed that the radiographic progression-free survival (rPFS) was over 16 months in the Abiraterone and prednisone group versus 8 months in the control group.
  2. Enzalutamide (Xtandi) – Formally known as MDV3100 this medication is second generation androgen-receptor blocker. It works both on the outside and inside of the cell. It was initially indicated in post-chemotherapy patients for mCRPC but studies have shown benefit in the pre-chemo patient also. The PREVAIL study showed that on average, enzalutamide delayed the need for chemotherapy by 17 months (28 vs 11). It also showed that use of this drug delayed radiographic progression by 81%.
  1. Radium 223 Dichloride (Xofigo) – Although this is an injection it is actually a type of radiation called alpha radiation. This treatment is meant to target prostate cancer cells in the bones.  Bones with prostate cancer preferentially absorb Xofigo. Radium then releases the alpha radiation, which is very short range. The idea is to kill the active cancer cells with minimal damage to normal bone. This should be more targeted than strontium-89, which has been used in the past. Studies have shown increased survival in patients with mCRPC and bone metastasis.
  1. Sipuleucel-T (Provenge) –  Sipuleucel-T is a therapeutic cancer vaccine for prostate cancer. It is meant for asymptomatic or minimally symptomatic patients with mCRPC. It is individualized to each patient and requires blood donation. The blood is activated at the lab and then re-infused later in the week. The treatment is provided 3 times over the period of a month. It is the first FDA approved therapeutic cancer vaccine (as opposed to a preventative vaccine). Overall survival was increased by the use of Provenge in symptomatic or minimally symptomatic mCRPC patients.

Questions to hopefully be clarified in the future are how to best sequence these new treatments? When a patient fails hormones, which medication should be used first or should chemo be initiated? Which medication provides the best value? Should these medications be used alone or in combination? While there are many questions outstanding these recent additions to the prostate cancer armamentarium will surely benefit many patients.

Sources 

Rathkopf DE, Smith MR, De Bono JS, et al. Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy. J Clin Oncol. 2013;31(suppl 6, abstr 5).

Beer TM et. al. Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study. J Clin Oncol  32, 2014 (suppl 4; abstr LBA1^).

Parker C et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. N Engl J Med. 2013; 369: 213.

Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". N. Engl. J. Med. 363 (5): 479–81.

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