BERKELEY, CA (UroToday.com) - The current landscape of treatment of castration-resistant prostate cancer (CRPC) has recently changed. Until 2004, docetaxel and androgen-deprivation therapy were the only treatments able to improve overall survival (OS). In the last two years, new trials have been published regarding the management of CRPC after docetaxel failure. Cabazitaxel, abiraterone acetate, sipuleucel-T, radium-223, and MDV3100 have been tested in phase III studies and positive results have been reported. For the first time, second-line therapies have been demonstrated to improve OS and the concept of sequential therapies in docetaxel-progressed CRPC has been introduced. The relevance of these trials is the reintroduction of chemotherapy and hormonal therapy in a disease once considered chemotherapy and castration resistant.
All of these data may change the traditional approach to CRPC, but so far no evidence has come out from the recently closed or ongoing clinical trials about the therapeutic algorithm. How to get oriented in this forest?
In this brief review we try to suggest a therapeutic algorithm for patients affected by CRPC after docetaxel failure. Medical oncologists have to evaluate performance status, response, and toxicities reported with previous treatments, disease burden, PSA kinetics, and the presence of symptoms. Based on these evaluations, clinicians can offer the best treatment for each patient.
The next goals in CRPC are to find out what is the best sequence after docetaxel failure and the selection of appropriate predictive factors of response to second-line therapies. References:
- Miyamoto H., Messing E.M., Chang C. (2004) Androgen deprivation therapy for prostate cancer: current status and future prospects. Prostate 61: 332–353.
- Tannock I.F., De Wit R., Berry W.R., Horti J., Pluzanska A., Chi K.N., et al. (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351: 1502–1512.
- De Bono J.S., Oudard S., Ozguroglu M., Hansen S., Machiels J.P., Koca K.I., et al. (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376: 1147–1154.
- De Bono J.S., Logothetis C.J., Molina A., Fizazi K., North S., Chu L., et al. (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364: 1995–2005.
- Kantoff P.W., Higano C.S., Shore N.D., Berger E.R., Small E.J., Penson D.F., et al. (2010) Sipuleucel-T immunotherapy for castration resistant prostate cancer. N Engl J Med 363: 411–422.
- Parker C., Heinrich D., O’Sullivan J.M., Fosså S., Chodacki A., Demkow T., et al. (2011) Overall survival benefit of Radium-223 Chloride (Alpharadin) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer (CRPC): a phase III randomised trial (ALSYMPCA). 2011 ESMO-ECCO Meeting, Abstract 1LBA.
- Scher H.I., Fizazi K., Saad F., Taplin M.E., Sternberg C.N., Miller M.D., et al. (2012) Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy. N Engl J Med, Epub ahead of print.
Amelia Altavilla, MD and Roberto Iacovelli, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
“Sapienza” University of Rome
Department of Radiology, Oncology and Human Pathology