ABSTRACT
BACKGROUND: Numerous globally approved castration-resistant prostate cancer (CRPC) therapies are available. Enzalutamide and radium 223 (Ra 223) are approved for survival prolongation and ability to delay radiographic progression. Both have markedly different mechanisms of action as well as safety and tolerability profiles. We prospectively investigated their combined safety and tolerability. PATIENTS AND METHODS: EnzaRadiCate, a phase II investigator-initiated trial, enrolled subjects with metastatic CRPC from 4 United States uro-oncology research sites. Safety assessment included physical examination, Eastern Cooperative Oncology Group status, electrocardiogram results, laboratory values, opioid use, radiographic responses, and adverse events (AEs). Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the Brief Pain Inventory Short Form (BPI-SF) questionnaires. RESULTS: Thirty-nine subjects completed at least 2 cycles of Ra 223, and 34 (87%) completed all 6 cycles through and the EOT visit. Sixty-one treatment-related AEs were reported by 53.8% of subjects. The most frequent AEs were fatigue (25.6%), nausea (17.9%), and anemia (12.8%). Three subjects experienced non-treatment-related serious AEs. One subject was hospitalized for sepsis, and 2 deaths were attributed to disease progression. Fifteen (38.5%) subjects demonstrated radiographic progression, and 24 (61.5%) subjects had no radiographic progression. CONCLUSIONS: Safety and tolerability of combinatorial use of enzalutamide and Ra 223 were demonstrated. Subjects experienced improvements in quality of life and pain, without unexpected toxicities nor increases in falls, fractures, or deaths. Phase III combination trials of Ra 223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Radium , Benzamides , Humans , Male , Nitriles , Phenylthiohydantoin/adverse effects , Prostatic Neoplasms, Castration-Resistant/drug therapy , Quality of Life , Radium/adverse effectsABSTRACT
BACKGROUND: Multiple castration-resistant prostate cancer (CRPC) therapies are approved by the United States Food and Drug Administration. Radium-223 dichloride (Ra-223) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off-target side-effect profiles. We prospectively investigated their combined safety, tolerability, and patient-reported outcome measures. PATIENTS AND METHODS: eRADicAte, an investigator-initiated, phase II trial, studied 31 patients with metastatic CRPC, from 5 United States uro-oncology research sites. Patients completed 6 cycles of Ra-223 with concurrent abiraterone therapy. Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form questionnaires and their subscales; we reported the number of subjects meeting standardized criteria for clinically meaningful improvements on each scale. Safety assessment included Eastern Cooperative Oncology Group performance status, laboratory changes, opioid use, radiographic responses, and adverse events (AEs). RESULTS: Twenty of 31 (65%) experienced positive clinically meaningful improvement changes on the Functional Assessment of Cancer Therapy-Prostate, and 25 (81%) of 31 on the Prostate Cancer Subscale. Eighteen (58%) of 31 demonstrated reduced pain intensity and 12 (39%) of 31 demonstrated reduction of pain interference in their lives. At baseline, subjects averaged 11.6 ± 2.8 bone lesions; at the end of treatment, subjects averaged 5.6 ± 2.4 bone lesions (P = .0002). The most frequent AEs were diarrhea (17%), nausea (17%), and fatigue (14%). There were 6 serious AEs; 1 led to study withdrawal. CONCLUSIONS: Patients experienced clinically meaningful improvements in quality of life and pain, without unexpected adverse toxicities. Phase III combination trials of Ra-223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit.
