Аннотация:Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer
By Evans, T. R. J. (Evans, T. R. J.) Van Cutsem, E. (Van Cutsem, E.) Moore, M. J. (Moore, M. J.) Bazin, I. S. (Bazin, I. S.) Rosemurgy, A. (Rosemurgy, A.) Bodoky, G. (Bodoky, G.) Deplanque, G. (Deplanque, G.) Harrison, M. (Harrison, M.) Melichar, B. (Melichar, B.) Pezet, D. (Pezet, D.) ...More
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ANNALS OF ONCOLOGY
Volume28
Issue2
Page354-361
DOI10.1093/annonc/mdw607
PublishedFEB 2017
Indexed2017-02-01
Document TypeArticle
Abstract
Background: 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.
Patients and methods: 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/m(2) (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.
Results: 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.
Conclusions: 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.
Keywords
Author Keywordsdasatinibgemcitabinepancreatic canceranticancer therapy
Keywords PlusCHRONIC MYELOID-LEUKEMIACYTOGENETIC RESPONSESIMATINIB-RESISTANTSRCADENOCARCINOMASURVIVALINHIBITIONBMS-354825
Addresses
1 Univ Glasgow, Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland
2 Univ Hosp Leuven, Dept Oncol, Leuven, Belgium
3 Katholieke Univ Leuven, Leuven, Belgium
4 Princess Margaret Canc, Toronto, ON, Canada
5 Fed State Budgetary Inst, Dubna, Russia
...more addresses
Categories/Classification
Research AreasOncology