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

Evans; (Evans, T.R.; Van Cutsem, T.R.; (Van Cutsem, E.; Moore, E.).; (Moore, M.J.; Bazin, M.J.; (Bazin, I.S.; Rosemurgy, I.S.; (Rosemurgy, A.; Bodoky, A.).; (Bodoky, G.; Deplanque, G.).; (Deplanque, G.; Harrison, G.).; (Harrison, M.; Melichar, M.).; (Melichar, B.; Pezet, B.).; (Pezet, D.; ), D.

Авторы: Evans, (Evans T.R.J, Van Cutsem T.R.J.), (Van Cutsem E., Moore E.)., (Moore M.J., Bazin M.J.), (Bazin I.S., Rosemurgy I.S.), (Rosemurgy A., Bodoky A.)., (Bodoky G., Deplanque G.)., (Deplanque G., Harrison G.)., (Harrison M., Melichar M.)., (Melichar B., Pezet B.)., (Pezet D., ) D.
Журнал: Annals of Oncology
Том: 28
Номер: 2
Год издания: 2017
Издательство: Oxford University Press
Местоположение издательства: United Kingdom
Первая страница: 354
Последняя страница: 361
DOI: 10.1093/ANNONC/MDW607
Аннотация: Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancerBy 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.) ...MoreView Web of Science ResearcherID and ORCID (provided by Clarivate) ANNALS OF ONCOLOGYVolume28Issue2Page354-361DOI10.1093/annonc/mdw607PublishedFEB 2017Indexed2017-02-01Document TypeArticleAbstractBackground: 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.KeywordsAuthor Keywordsdasatinibgemcitabinepancreatic canceranticancer therapyKeywords PlusCHRONIC MYELOID-LEUKEMIACYTOGENETIC RESPONSESIMATINIB-RESISTANTSRCADENOCARCINOMASURVIVALINHIBITIONBMS-354825Addresses1 Univ Glasgow, Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland2 Univ Hosp Leuven, Dept Oncol, Leuven, Belgium3 Katholieke Univ Leuven, Leuven, Belgium4 Princess Margaret Canc, Toronto, ON, Canada5 Fed State Budgetary Inst, Dubna, Russia...more addressesCategories/ClassificationResearch AreasOncology
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Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancerстатья