State-of-the-art lecture: beyond the androgen receptor
Unfortunately, these castration-resistant PCa (CRPC) are almost uniformly lethal within a few months, not before having induced morbid complications, including painful skeletal events (SRE). Although understanding and bypassing the process of resistance to castration has been one of most important topic for basic and clinical research in genitourinary oncology, it took more than 50 years before active drugs were produced.In 2004 indeed, three major breakout studies were published in CRPC showing that the taxane docetaxel improves overall survival (OS) by about three months and that the bisphosphonate zoledronic acid could effectively delay the occurrence of skeletal related events in men with bone metastases (Tannock et al. NEJM 2004; Petrylak et al. NEJM 2004; Saad et al. JNCI 2004).
Needless to say that these two agents have profoundly impacted the day-to-day care of CRPC patients, firstly by giving new hopes to these patients but, maybe more importantly, by pushing urologists to revisit the collaboration with medical oncologist.
Rapidly, however, it appeared this would only provide transient relief from the disease and that new agents were required. Interestingly, all these promising agents came a few months apart from each other in 2010.
Cabazitaxel is a novel taxane that retains activity in docetaxel resistant prostate cancer cells. Cabazitaxel has been compared to mitoxantrone in patients with metastatic CRPC who progressed after docetaxel. Cabazitaxel extended OS from 12.7 months in the mitoxantrone group to 15.1 months (p<0•0001). Neutropenia was observed in 82% of the patients receiving cabazitaxel, including 8% of febrile neutropenia (de Bono et al, Lancet 2010).
Sipuleucel-T is a dendritic cell -based vaccine, that uses the patient’s own dendritic cells to produce a immune response against CRPC cells. The vaccine is tailored to each patient after a complex process of extraction and genetic engineering. A phase III study vs. a sham procedure has showed that sipuleucel-T increased survival by 4.1 month in asymptomatic or minimally symptomatic metastatic CRPC (Kantoff PW et al, NEJM 2010).
Beyond the simple clinical results, the Sipuleucel-T study is remarkable because it demonstrates that turning the patient’s own immunity against the cancer is no longer science fiction. This vaccine is the first FDA-approved vaccine for advanced cancer.
Read the full version of this article in EUT Congress News which will be published and distributed at the congress.
Sunday, 20 March 2011Plenary Session 2High risk prostate cancer07.30 -11.00