Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer.

Détails

ID Serval
serval:BIB_50D2E9A71929
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer.
Périodique
Annals of oncology
Auteur(s)
Evans TRJ, Van Cutsem E., Moore M.J., Bazin I.S., Rosemurgy A., Bodoky G., Deplanque G., Harrison M., Melichar B., Pezet D., Elekes A., Rock E., Lin C., Strauss L., O'Dwyer P.J.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Statut éditorial
Publié
Date de publication
01/02/2017
Peer-reviewed
Oui
Volume
28
Numéro
2
Pages
354-361
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
Publication Status: ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC.
This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate.
There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm.
Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

Mots-clé
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carcinoma, Pancreatic Ductal/drug therapy, Carcinoma, Pancreatic Ductal/mortality, Carcinoma, Pancreatic Ductal/pathology, Dasatinib/administration & dosage, Deoxycytidine/administration & dosage, Deoxycytidine/analogs & derivatives, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms/drug therapy, Pancreatic Neoplasms/mortality, Pancreatic Neoplasms/pathology, Proportional Hazards Models, Treatment Outcome, anticancer therapy, dasatinib, gemcitabine, pancreatic cancer
Pubmed
Web of science
Création de la notice
29/12/2016 9:37
Dernière modification de la notice
03/03/2018 17:09
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