Phase I Trial of DNA Methyltransferase Inhibitor Guadecitabine Combined with Cisplatin and Gemcitabine for Solid Malignancies Including Urothelial Carcinoma (SPIRE).
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Azacitidine
/ administration & dosage
Carcinoma, Transitional Cell
/ drug therapy
Cisplatin
/ administration & dosage
Deoxycytidine
/ administration & dosage
Female
Granulocyte Colony-Stimulating Factor
/ therapeutic use
Humans
Male
Middle Aged
Urinary Bladder Neoplasms
/ drug therapy
Gemcitabine
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
12
10
2020
revised:
22
12
2020
accepted:
15
01
2021
pubmed:
22
1
2021
medline:
11
3
2022
entrez:
21
1
2021
Statut:
ppublish
Résumé
Preclinical data indicate that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers. SPIRE comprised a dose-escalation phase for incurable metastatic solid cancers, followed by a randomized dose expansion phase for neoadjuvant treatment of T2-4a N0 M0 bladder urothelial carcinoma. The primary objective was a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin. Treatment comprised 21-day gemcitabine and cisplatin cycles (cisplatin 70 mg/m Within the escalation phase, dose-limiting toxicities related predominantly to myelosuppression requiring G-CSF prophylaxis from cohort 2 (guadecitabine 20 mg/m The guadecitabine RP2D was 20 mg/m
Identifiants
pubmed: 33472913
pii: 1078-0432.CCR-20-3946
doi: 10.1158/1078-0432.CCR-20-3946
pmc: PMC7611191
mid: EMS128741
doi:
Substances chimiques
Deoxycytidine
0W860991D6
Granulocyte Colony-Stimulating Factor
143011-72-7
guadecitabine
2KT4YN1DP7
Azacitidine
M801H13NRU
Cisplatin
Q20Q21Q62J
Gemcitabine
0
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
1882-1892Subventions
Organisme : Cancer Research UK
ID : A19903
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR300047
Pays : United Kingdom
Informations de copyright
©2021 American Association for Cancer Research.
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