Phase II trial exploring the combination of enzalutamide with five alpha-reductase inhibitors (ARIs) for castrate-sensitive prostate cancer. Driven by observations from geriatric oncology, the study seeks alternatives to androgen deprivation therapy (ADT) for older, frail men who struggle with its side effects. The trial examines whether enzalutamide combined with dutasteride or finasteride can effectively manage prostate cancer while avoiding ADT. The results are promising, showing a median PSA progression-free survival that was not reached, with many patients maintaining low PSA levels for several years. Despite side effects like fatigue and gynecomastia, the treatment is well tolerated. The study highlights the potential for using ARIs and enzalutamide in this vulnerable group, suggesting a shift towards less intensive therapies could benefit frail patients.
This further supports the use of androgen receptor blockers with ARIs. Bicalutamide has long been used for this (though still under utilized). It blocks the ARs effectively at both 50mg and 150mg/day doses. This tricks the hypothalamus into responding to a perceived low testosterone levels and secretes more Luteinizing hormone, so the testes put out higher testosterone levels. Even though blocked the side effect profile is much better than with ADT by Lupron and similar. The ARI is added to block conversion of the testosterone to DHT. Dutasteride (Avodart) at 1.0 mg/day works nicely.
These regimens, whether with biclutamide or enzalutamide can thus provide an effective alternative to Lupron ADT for years. PSA must be monitored because eventually the AR receptors can mutate to being stimulated rather than blocked by the regimen. PSA will rise and it must be discontinued. Often the PSA will drop back down when it is stopped. This regimen worked for me, without Lupron ADT for 4+ years.
Tbe high testosterone levels while on this can be converted to estradiol and lead to gynecomastia. This can be managed by either irradiating the breast tissue before starting, or with Tamoxifen daily. Paul/MB
This is a very exciting study, with important results! People need to know there are alternatives to standard ADT, especially for older men who may be frail. Thank you for posting it.
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