Older men are at risk for adverse events (AEs) from androgen deprivation therapy (ADT). In prior studies, peripheral androgen blockade with bicalutamide and Fin was better tolerated but less efficacious than ADT in HNSPCa. The potential synergism of Enz and Dut/Fin provided the rationale for this Phase II study.
Eligible subjects were ≥ 65 yrs; at risk of AEs from ADT as determined by treating physicians; had metastatic (M1) or non-metastatic (M0) HNSPCa with a PSA doubling time 50 ng/dl. Enz (160mg daily) with Dut (0.5mg daily) or Fin (5mg daily) was given until progression per the Prostate Cancer Working Group 2 guidelines or unacceptable AEs. Comprehensive geriatric assessment (CGA) was done at baseline and every 4 months. The primary endpoint is time to PSA progression. The secondary endpoints are time to PSA nadir, AEs, and effects on CGA domains.
As of 4/15/17, we completed study enrollment of 40 subjects. Herein, we report outcomes of the first 31 subjects with a median follow-up of 43 weeks. Median age at enrollment was 80 yrs. 29%, 61%, and 10% had ECOG performance status of 0, 1, and 2, respectively. 45% had M0 and 55% had M1 HNSPCa. Gleason’s sum was 6, 7, >8, and unknown in 19%, 49%, 23%, and 9%, respectively. At enrollment; the median PSA was 12.71 ng/ml. CGA showed cognitive impairment in 61%, physical impairment in 54%, depression in 16% and impairment of instrumental activities of daily living in 13%. The median time to 90% PSA decline was 7 weeks. 79% of patients had 80% DHT decline by 9 months. At the time of analysis, all patients had PSA decline of > 90% without radiographic evidence of disease progression. Baseline CGA did not correlate with efficacy (P-values >0.1). Common Grade 1 AEs included gynecomastia (26%), fatigue (35%), hot flashes (22%) and paresthesia (13%). None had Grade 3 or 4 AEs. Three men withdrew from the study due to treatment-related AEs (Grade 2 fatigue and paresthesia). Another three patients withdrew due to unrelated issues.
Enz with Dut/Fin appears to be safe and efficacious for older patients with M0 and M1 HNSPCa. Future research will report effects of treatment on CGA domains.
Clinical trial identification
Legal entity responsible for the study
University of Rochester
Astellas and Pfizer Inc
All authors have declared no conflicts of interest.