Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients.
Clin Cancer Res
; 24(24): 6345-6354, 2018 12 15.
Article
em En
| MEDLINE
| ID: mdl-30154226
ABSTRACT
PURPOSE:
Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment. EXPERIMENTALDESIGN:
We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options.RESULTS:
The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy.CONCLUSIONS:
Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Resistencia a Medicamentos Antineoplásicos
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Desoxicitidina
/
Imunomodulação
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Antineoplásicos Imunológicos
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Neoplasias Pulmonares
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Mesotelioma
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article