A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer.
Oncology
; 96(4): 217-222, 2019.
Article
em En
| MEDLINE
| ID: mdl-30844808
ABSTRACT
OBJECTIVES:
Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor.METHODS:
This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone.RESULTS:
Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS 3.7 months, OS 5.7 months) and those treated with gemcitabine alone (PFS 1.9 months, OS 5.6 months).CONCLUSIONS:
Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Benzimidazóis
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Coagulação Sanguínea
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Protocolos de Quimioterapia Combinada Antineoplásica
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Fator VIIa
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Ácido Aspártico
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Carcinoma Ductal Pancreático
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Desoxicitidina
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Anticoagulantes
Tipo de estudo:
Clinical_trials
Limite:
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:
Oncology
Ano de publicação:
2019
Tipo de documento:
Article