Pazopanib and Fosbretabulin in recurrent ovarian cancer (PAZOFOS): A multi-centre, phase 1b and open-label, randomised phase 2 trial.
Angiogenesis Inhibitors
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Carcinoma, Ovarian Epithelial
/ blood
Cardiotoxicity
/ etiology
Dose-Response Relationship, Drug
Female
Humans
Indazoles
Neoplasm Recurrence, Local
Neovascularization, Pathologic
/ blood
Ovarian Neoplasms
/ blood
Progression-Free Survival
Pyrimidines
/ adverse effects
Stilbenes
/ administration & dosage
Sulfonamides
/ adverse effects
Survival Rate
Fosbretabulin
Ovarian cancer
Pazopanib
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
20
11
2019
revised:
30
12
2019
accepted:
02
01
2020
pubmed:
15
1
2020
medline:
3
7
2020
entrez:
15
1
2020
Statut:
ppublish
Résumé
Vascular co-option is a resistance mechanism to anti-angiogenic agents, but combinations of anti-vascular agents may overcome this resistance. We report a phase 1b and randomised phase 2 trial to determine the safety and efficacy of pazopanib with fosbretabulin. Eligible patients had recurrent, epithelial ovarian cancer with a platinum-free interval (PFI) of 3 to 12 months. Patients were stratified according to PFI (>6 versus ≤6 months) and prior bevacizumab use. Twelve patients were treated in the phase 1b. Commonest grade ≥ 2 adverse events (AEs) were hypertension (100%), neutropenia (50%), fatigue (50%), vomiting (50%). There was one DLT (grade 3 fatigue). The recommended phase 2 dose level was fosbretabulin 54 mg/m It remains unclear whether pazopanib with with fosbretabulin is an efficacious regimen to treat epithelial ovarian cancer. Effective cardiac risk mitigation is needed to increase the tolerability and maximize patient safety in future trials.
Identifiants
pubmed: 31932108
pii: S0090-8258(20)30005-6
doi: 10.1016/j.ygyno.2020.01.005
pii:
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Indazoles
0
Pyrimidines
0
Stilbenes
0
Sulfonamides
0
pazopanib
7RN5DR86CK
fosbretabulin
I5590ES2QZ
Banques de données
ClinicalTrials.gov
['NCT02055690']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
545-551Subventions
Organisme : Cancer Research UK
ID : CRUKE/13/022
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interest.