Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial.
Castration-resistant prostate cancer
Combination treatment
Docetaxel
Radium 223 dichloride
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
29
01
2019
revised:
21
03
2019
accepted:
02
04
2019
pubmed:
15
5
2019
medline:
30
5
2020
entrez:
15
5
2019
Statut:
ppublish
Résumé
Radium 223 dichloride (radium-223) is an alpha particle-emitting bone-directed therapy that prolongs overall survival in men with bone-predominant metastatic castration-resistant prostate cancer (mCRPC). Docetaxel is an antimicrotubule cytotoxic agent that improves survival in mCRPC. We investigated whether combining these potentially cross-sensitising agents to dually target tumour and bone would be safe and effective. Phase 1 was a dose escalation study to define a recommended phase 2 dose (RP2D) of docetaxel and radium-223. In phase 2a, patients were randomised 2:1 to the recommended combination regimen or docetaxel at a dose of 75 mg/m Twenty patients were enrolled in phase 1; 53 patients were randomised in phase 2a: 36 to combination treatment and 17 to docetaxel alone. The RP2D for the combination was radium-223 55 kBq/kg every six weeks × 5 doses, plus docetaxel 60 mg/m Radium-223 in combination with docetaxel at the RP2D was well tolerated. Exploratory efficacy data suggested enhanced antitumour activity for the combination relative to docetaxel alone. Comparative studies with end-points of clinical benefit are warranted. ClinicalTrials.gov number: NCT01106352.
Identifiants
pubmed: 31082669
pii: S0959-8049(19)30240-0
doi: 10.1016/j.ejca.2019.04.007
pmc: PMC7474951
mid: NIHMS1621413
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Docetaxel
15H5577CQD
Radium-223
8BR2SOL3L1
Radium
W90AYD6R3Q
Banques de données
ClinicalTrials.gov
['NCT01106352']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-116Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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