Re-treatment with radium-223 : 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases

Autor: Luke T. Nordquist, Avivit Peer, Kalevi Pulkkanen, Oliver Sartor, Stefano Severi, Daniel Keizman, Giuseppe Procopio, Camilla Thellenberg Karlsson, Stephen Frank, Neil Mariados, Eli Rosenbaum, Rui Li, María José Méndez Vidal, José Trigo, Volker Wagner, Daniel Heinrich, Lucia Trandafir
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
SSEs
chemistry.chemical_compound
Prostate cancer
0302 clinical medicine
Urologi och njurmedicin
Aged
80 and over
Abiraterone acetate
Middle Aged
Survival Rate
Prostate-specific antigen
Prostatic Neoplasms
Castration-Resistant
Oncology
030220 oncology & carcinogenesis
Disease Progression
Original Article
alkaline phosphatase
medicine.drug
Radium
Radium-223
safety
medicine.medical_specialty
Urology
Antineoplastic Agents
Bone Neoplasms
survival
03 medical and health sciences
Internal medicine
medicine
Enzalutamide
Humans
prostate-specific antigen
Urology and Nephrology
Adverse effect
Aged
Radioisotopes
Chemotherapy
Cancer och onkologi
business.industry
Original Articles
Prostate-Specific Antigen
symptomatic skeletal events
medicine.disease
030104 developmental biology
chemistry
Concomitant
Cancer and Oncology
prostate‐specific antigen
business
Follow-Up Studies
Zdroj: The Prostate
Popis: Background Radium‐223 dichloride (radium‐223) is approved for patients with castration‐resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open‐label, phase 1/2 study NCT01934790 showed that re‐treatment with radium‐223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2‐year follow‐up of the radium‐223 re‐treatment study. Methods Patients with CRPC and bone metastases who completed 6 initial radium‐223 injections with no disease progression in bone and later progressed were eligible for radium‐223 re‐treatment (up to 6 additional radium‐223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium‐223. Concomitant cytotoxic agents were not allowed during re‐treatment but were allowed at the investigator's discretion during follow‐up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression‐free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate‐specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE‐free survival, all calculated from re‐treatment start. Evaluation of safety and exploratory efficacy objectives included active 2‐year follow‐up. Safety results from active follow‐up and updated efficacy are reported. Results Overall, 44 patients were re‐treated with radium‐223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2‐year active follow‐up, during which no new safety concerns and no serious drug‐related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE‐free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions Re‐treatment with radium‐223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2‐year follow‐up.
Databáze: OpenAIRE
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