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A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors

Candelaria, M ; Gallardo-Rincón, D ; Arce, C ; Cetina, L ; Aguilar-Ponce, JL ; Arrieta, Ó ; González-Fierro, A ; Chávez-Blanco, A ; de la Cruz-Hernández, E ; Camargo, MF ; Trejo-Becerril, C ; Pérez-Cárdenas, E ; Pérez-Plasencia, C ; Taja-Chayeb, L ; Wegman-Ostrosky, T ; Revilla-Vazquez, A ; Dueñas-González, A

Annals of oncology, 2007-09, Vol.18 (9), p.1529-1538 [Periódico revisado por pares]

Oxford: Oxford University Press

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Título:
A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors
Autor: Candelaria, M ; Gallardo-Rincón, D ; Arce, C ; Cetina, L ; Aguilar-Ponce, JL ; Arrieta, Ó ; González-Fierro, A ; Chávez-Blanco, A ; de la Cruz-Hernández, E ; Camargo, MF ; Trejo-Becerril, C ; Pérez-Cárdenas, E ; Pérez-Plasencia, C ; Taja-Chayeb, L ; Wegman-Ostrosky, T ; Revilla-Vazquez, A ; Dueñas-González, A
Assuntos: Adolescent ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; DNA Methylation ; Drug Resistance, Neoplasm ; Epigenesis, Genetic ; epigenetic therapy ; Female ; Histone Deacetylases - metabolism ; Humans ; hydralazine ; Hydralazine - administration & dosage ; Hydralazine - adverse effects ; Hydralazine - blood ; magnesium valproate ; Male ; Medical sciences ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasms - drug therapy ; Neoplasms - genetics ; Pharmacology. Drug treatments ; phase II ; refractory ; solid tumors ; Tumors ; Valproic Acid - administration & dosage ; Valproic Acid - adverse effects ; Valproic Acid - blood
É parte de: Annals of oncology, 2007-09, Vol.18 (9), p.1529-1538
Notas: ark:/67375/HXZ-CWM5H3BB-H
istex:BA4766DEC460D8E1E3180AA5D0A9C6452F08F8F9
ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Background: Epigenetic aberrations lead to chemotherapy resistance; hence, their reversal by inhibitors of DNA methylation and histone deacetylases may overcome it. Patients and methods: Phase II, single-arm study of hydralazine and magnesium valproate added to the same schedule of chemotherapy on which patients were progressing. Schedules comprised cisplatin, carboplatin, paclitaxel, vinorelbine, gemcitabine, pemetrexed, topotecan, doxorubicin, cyclophosphamide, and anastrozole. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow, acetylators, and magnesium valproate at 40 mg/kg, beginning a week before chemotherapy. Response, toxicity, DNA methylation, histone deacetylase activity, plasma valproic acid, and hydralazine levels were evaluated. Results: Seventeen patients were evaluable for toxicity and 15 for response. Primary sites included cervix (3), breast (3), lung (1), testis (1), and ovarian (7) carcinomas. A clinical benefit was observed in 12 (80%) patients: four PR, and eight SD. The most significant toxicity was hematologic. Reduction in global DNA methylation, histone deacetylase activity, and promoter demethylation were observed. Conclusions: The clinical benefit noted with the epigenetic agents hydralazine and valproate in this selected patient population progressing to chemotherapy’ and re-challenged with the same chemotherapy schedule after initiating hydralazine and valproate’ lends support to the epigenetic-driven tumor-cell chemoresistance hypothesis (ClinicalTrials.gov Identifier: NCT00404508).
Editor: Oxford: Oxford University Press
Idioma: Inglês

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A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors

Oxford: Oxford University Press

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