Low Dose Enzalutamide in the Late-Elderly Patient (≥75 years old) presenting with Metastatic Castration-Resistant Prostate Cancer

Abstract Background Enzalutamide, a major anti-androgen indicated for metastatic castration-resistant prostate cancer has worrisome toxicities in ageing patients. Dose-reduction might limit toxicity, but potential loss of efficacy is a concern. We compare upfront low-dose versus standard dose enzalutamide. Patients and Methods Records of prostate cancer patients receiving enzalutamide were retrospectively retrieved. Selection criteria were: age ≥75, metastatic disease, surgical or medical castration, and rising prostate specific antigen (PSA). Cases missing follow-up PSA were excluded. Low-dose enzalutamide (≤80 mg/day) was compared with standard dose (160 mg/day). Progression-free survival analyzed time from start of enzalutamide to event defined as ≥25% and ≥2 ng/ml PSA increase above nadir, or death from any cause. Results Fifty-nine patients were identified, of whom 16 received low-dose, 43 standard dose. Low-dose patients were significantly old, median age 84.6 years (range, 74.9–93.8); median PSA at start enzalutamide was 59.2 ng/mL (11.0–1058.3); 11 had bone metastases only, 2 metastatic lymph nodes only, 3 bone and lymph nodes localizations. Pain score was >3/10 in 4 patients (27%), ECOG performance status was ≥2 in 9 (56%); 3 patients received prior abiraterone and 3, bicalutamide. None had chemotherapy. PSA decrease of ≥ 50% at 12 weeks was observed in 67% (10/15) patients, versus 45.0% with standard dose. Median PSA at last follow-up was 1.6 ng/ml (0.0–599.3). Median progression-free survival was 11.2 months, versus 11.9 months standard-dose, P=0.612. Conclusion Low-dose enzalutamide in very-old, symptomatic, poor-performance metastatic patients was associated with high response-rate and survival comparable to standard dose.