Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Carboplatin
/ pharmacology
Carcinoma, Transitional Cell
/ drug therapy
Chemotherapy-Induced Febrile Neutropenia
/ epidemiology
Cisplatin
/ pharmacology
Drug Resistance, Neoplasm
Fatigue
/ chemically induced
Female
Humans
Hypertension
/ chemically induced
Hyponatremia
/ chemically induced
Kaplan-Meier Estimate
Male
Maximum Tolerated Dose
Middle Aged
Neutropenia
/ chemically induced
Sorafenib
/ administration & dosage
Urinary Bladder Neoplasms
/ drug therapy
Vinblastine
/ administration & dosage
Young Adult
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
12
10
2018
accepted:
15
11
2018
pubmed:
16
12
2018
medline:
21
7
2020
entrez:
16
12
2018
Statut:
ppublish
Résumé
First trial to report safety and activity of the microtubule inhibitor vinflunine plus the tyrosine kinase inhibitor sorafenib in post-platinum metastatic urothelial cancer (mUC) patients.A recommended phase II dose was identified for the treatment combination of vinflunine plus sorafenib, with main adverse events including fatigue, febrile neutropenia, neutropenia, hypertension, and hyponatremia.An overall response rate of 41% to second-line vinflunine plus sorafenib treatment in patients with platinum-resistant mUC was confirmed. Platinum-progressive metastatic urothelial carcinoma (mUC) is a clinical challenge. The tyrosine kinase inhibitor sorafenib has demonstrated varied activity in mUC. This trial was designed to examine safety and activity of vinflunine plus sorafenib in mUC. In addition to standard dose of vinflunine (320 or 280 mg/m Twenty-two patients (median age 62.5 years) were included. Five patients received vinflunine 320 mg/m The defined recommended phase II dose (RPTD) was vinflunine 280 mg/m
Sections du résumé
LESSONS LEARNED
First trial to report safety and activity of the microtubule inhibitor vinflunine plus the tyrosine kinase inhibitor sorafenib in post-platinum metastatic urothelial cancer (mUC) patients.A recommended phase II dose was identified for the treatment combination of vinflunine plus sorafenib, with main adverse events including fatigue, febrile neutropenia, neutropenia, hypertension, and hyponatremia.An overall response rate of 41% to second-line vinflunine plus sorafenib treatment in patients with platinum-resistant mUC was confirmed.
BACKGROUND
Platinum-progressive metastatic urothelial carcinoma (mUC) is a clinical challenge. The tyrosine kinase inhibitor sorafenib has demonstrated varied activity in mUC. This trial was designed to examine safety and activity of vinflunine plus sorafenib in mUC.
METHODS
In addition to standard dose of vinflunine (320 or 280 mg/m
RESULTS
Twenty-two patients (median age 62.5 years) were included. Five patients received vinflunine 320 mg/m
CONCLUSION
The defined recommended phase II dose (RPTD) was vinflunine 280 mg/m
Identifiants
pubmed: 30552156
pii: theoncologist.2018-0795
doi: 10.1634/theoncologist.2018-0795
pmc: PMC6656519
doi:
Substances chimiques
vinflunine
5BF646324K
Vinblastine
5V9KLZ54CY
Sorafenib
9ZOQ3TZI87
Carboplatin
BG3F62OND5
Cisplatin
Q20Q21Q62J
Banques de données
ClinicalTrials.gov
['NCT01844947']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
745-e213Informations de copyright
© AlphaMed Press; the data published online to support this summary are the property of the authors.
Références
N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Lancet. 2016 May 7;387(10031):1909-20
pubmed: 26952546
Lancet Oncol. 2017 Mar;18(3):312-322
pubmed: 28131785
Lancet Oncol. 2018 Jan;19(1):51-64
pubmed: 29217288
Invest New Drugs. 2018 Aug;36(4):615-618
pubmed: 29081023
Ann Oncol. 2016 Mar;27(3):449-54
pubmed: 26673352
Lancet. 2017 Nov 18;390(10109):2266-2277
pubmed: 28916371
J Clin Oncol. 2009 Sep 20;27(27):4454-61
pubmed: 19687335
Br J Cancer. 2006 May 22;94(10):1395-401
pubmed: 16622447
Lancet. 2014 Jul 26;384(9940):319-28
pubmed: 24768112
Anticancer Drugs. 2013 Apr;24(4):422-5
pubmed: 23407060
Cancer. 2009 Sep 15;115(18):4110-7
pubmed: 19536904
J Clin Oncol. 2009 Mar 10;27(8):1280-9
pubmed: 19171708
BJU Int. 2014 Mar;113(3):429-36
pubmed: 24053564
JAMA Oncol. 2017 Sep 14;3(9):e172411
pubmed: 28817753
N Engl J Med. 2017 Mar 16;376(11):1015-1026
pubmed: 28212060