Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer.
Ann Oncol
; 28(2): 354-361, 2017 02 01.
Article
en En
| MEDLINE
| ID: mdl-27998964
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 andmethods:
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.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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
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2_ODS3
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6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_nao_transmissiveis
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2_muertes_prematuras_enfermedades_notrasmisibles
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6_endocrine_disorders
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6_pancreatic_cancer
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6_sense_organ_diseases
Asunto principal:
Neoplasias Pancreáticas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Ductal Pancreático
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido