Editing Castrate-Resistant Prostate Cancer (section)

====== Radium-223 ======
* '''MOA: Alpha-emitting radiopharmaceutical'''
* '''Indications'''
** '''mCRPC, pain from bone metastasis AND no evidence of visceral metastasis AND no bulky (>3cm) lymph-node metastases, pre- or post-docetaxel'''
* '''Adverse events'''
** '''Lymphocytopenia'''
* '''A bone-supportive agent (denosumab or zoledronic acid) should always be used in mCRPC (see below), but especially when using radium-223'''
* '''PSA measurements while receiving radium-223 cannot provide evidence of whether patients are benefitting or not.'''§
** '''Given the mechanism of action of the drug, alkaline phosphatase appears to be better marker of activity.'''
* '''ALSYMPCA'''
** '''Population''': 921 '''men with symptomatic and progressive mCRPC with or without prior docetaxel and no evidence of visceral metastasis or bulky (>3cm) lymph-node metastases'''
** '''Randomized to radium-223 vs. placebo'''
** Primary outcome: OS
** Results:
*** '''OS improved by 4 months''' (14.9 months radium-223 vs. 11.3 months placebo, HR 0.70) in Radium-223 arm
*** Time to first SRE improved from 9.8 month with placebo to 15.6 months with radium-223 (HR=0.66). Significant improvements in QOL measurements were reported in the patients treated with radium-223.
*** Rates of grade 3 or 4 neutropenia and thrombocytopenia were low at 2.2% and 6.3%, respectively. Diarrhea was the most common side effect in 223Ra-treated patients
** Parker, Christopher, et al."Alpha emitter radium-223 and survival in metastatic prostate cancer." ''New England Journal of Medicine'' 369.3 (2013): 213-223.
* '''Should not be combined with abiraterone'''
** ERA 223 was a RCT that compared the combination of radium-223 with abiraterone/prednisone vs. abiraterone/prednisone alone and in the first-line mCRPC setting demonstrated no advantage and an increased risk of fractures§