Do the newer agents for ADT add to the cardiovascular risk of the LHRH drugs?

This is a meta-analysis of five randomized control trials involving 6735 patients, all with advance (i.e., castrate resistant) disease. All these patients had been on LHRH drugs and were in trials to evaluate the benefits and risks of either enzalutimide (Xtandi) or CYP-17 inhibitors, specifically abiraterone (Zytiga) or Tak 700 (Orteronel). Treatment with these new agents increased the risk of high-grade cardiovascular toxicity, such as a myocardial infarction—with the CYP-17 inhibitors showing disproportionately higher grade adverse events than the other treatments. It should be noted though that the CYP-17 inhibitors are taken with a corticosteroid, which might exacerbate cardiovascular toxicity. Furthermore these patients were concurrently on standard LHRH drugs and, as the authors noted, that their "analysis was unable to explore whether this combination has and additive or multiplicative effect on toxicity."


Iacovelli R, Verri E, Cossu Rocca M, Aurilio G, Cullura D, De Cobelli O, Nole F. 2015. The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer. Eur J Cancer 51(14):1970-1977.