Clinical and Preclinical Treatment Aspects of Castration Resistant Prostate Cancer (CRPC)
(Klinische en preklinische aspecten van behandeling bij castratie resistent prostaatcarcinoom)
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In the Western countries prostate cancer is the most frequently diagnosed cancer, except for skin cancer, and the second leading cause of male cancer deaths. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many patients may never have symptoms, undergo no therapy, and eventually die from other causes. This is because cancer of the prostate is, in many cases, slow-growing, symptom-free, and since men with the condition are older they often die from causes unrelated to the prostate cancer. Men diagnosed with clinically localized prostate cancer have several treatment options available, including watchful waiting, definitive radiation therapy and surgery. However, a significant proportion of patients who present with cancer that appears to be localized will eventually develop incurable metastatic disease and ultimately succumb to death as a result of advanced disease. In patients with advanced disease androgen-deprivation therapies typically result in rapid responses, but eventually nearly all patients develop progressive castration-resistant disease. Historically, clinical management for metastatic castration resistant prostate cancer (CRPC) has been primarily focused on relieving symptoms. In the last decade the therapeutic spectrum has changed dramatically, and our understanding of the biology of patients with prostate cancer has become far more sophisticated. The treatment paradigm first changed with the publication of 2 pivotal randomized clinical trials in 2004, which demonstrated for the first time a survival benefit with docetaxel-based therapy in patients with metastatic CRPC. Since then, docetaxel chemotherapy has become the standard first-line treatment in patients with CRPC (Chapter 2). Recently, the landscape for CRPC treatment has changed again with the FDA approval of three additional therapies, sipuleucel-T5, cabazitaxel6 and abiraterone acetate7. While the addition of these new treatment options is a great advance for patients with metastatic CRPC, there are many new questions arising regarding the optimal sequencing of these treatments as well as potential combinations of and old drugs.
The research for this thesis was financially supported by: Amgen B.V., Astellas Pharma B.V., Bayer B.V., Boehringer Ingelheim B.V., Celgene B.V., Janssen-Cilag B.V., J.E. Juriaanse Stichting, MSD B.V., Novartis Pharma B.V., Pfizer B.V., Roche Nederland B.V., Sanofi-aventis Netherlands B.V.
- prostate cancer