Salvage Radiation Therapy and Enzalutamide: A Winning Combination?
The vast majority of the estimated 30,000 American men who will die of prostate cancer this year originally were treated for localized prostate cancer with radical prostatectomy or radiation, but the cancer came back and spr ead. “When the PSA initially comes back after surgery, this is the time when these men are still potentially curable with salvage radiation,” says Phuoc T. Tran, M.D., Ph.D., Associate Professor of Radiation Oncology and Molecular Radiation Sciences, Oncology and Urology.
The window of curability is still open for these men, Tran says, and he wants to maximize their chances of cur e. “Salvage radiotherapy is the mainstay of treatment for men with a persis tently detectable PSA or a delayed rise in PSA without evidence of metastasis,” he notes. “But it is clear that salv age radiotherapy alone is not lik ely to guarantee freedom from PSA progression or cure in most high-risk men.” Tran hopes that adding drugs that target the androgen, or male hormone, receptors to salvage radiation therapy will prove to be the winning combination to knocking out the cancer while it is s till curable.
Androgen receptor-blocking drugs impair growth in the majority of prostate cancers, and androgen deprivation (hormonal therapy) drugs also kill many prostate cancer cells; however, “those cells that do not die will ultimately become resistant and will grow despite androgen deprivation,” says Tran. Several randomized trials have shown that hormonal therapy improves overall survival in men who are receiving primary radiation therapy for prostate cancer. “But there is no consensus on how to apply androgen deprivation, or which patients undergoing salvage radiotherapy would benefit most.” The drug bicalutamide, a first-generation androgen receptor blocker, has been used successfully in combination with salvage radiation therapy.
But enzalutamide, a second-generation androgen receptor blocker, looks even more promising, Tran says. “Enzalutamide significantly prolongs survival in patients with metastatic, castrationresistant prostate cancer given either before docetaxel chemotherapy or even after.” Enzalutamide is taken orally and is generally well tolerated, “which makes it an ideal candidate for combi - nation with salvage radiotherapy. Also, provocative preliminary Phase II data presented at the American Society of Clinical Oncology’s annual meeting in 2013” by medical oncologists at Massachusetts General Hospital “assessed the efficacy and safety of six months of enzalutamide alone in men with prostate cancer of all stages who had never received hormonal therapy. Enzalutamide alone for six months achieved a high PSA response rate, but in contrast to hormonal therapy had much fewer side effects.”
“Our hope with this trial is to improve outcomes in highrisk men with biochemical failure following radical prostatectomy, and to significantly reduce the number of men who die of prostate cancer each year.”
Tran and medical oncologist Emmanuel Antonarakis will soon be launching a multicenter, randomized Phase II clinical study of salvage radiation therapy with or without enzalutamide in men who have a detectable or rising PSA after radical prostatectomy. “This trial will allow us to determine the efficacy of adding a second-generation androgen receptor blocker with salvage radiation therapy,” says Tran. “Our hope with this trial is to impr ove outcomes in high-risk men with biochemical failure following radical prostatectomy, and to significantly reduce the number of men who die of prostate cancer each year.”