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Medical Oncology

, Volume 28, Supplement 1, pp 540–546 | Cite as

A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results

  • Jaime Coronel
  • Lucely Cetina
  • Irlanda Pacheco
  • Catalina Trejo-Becerril
  • Aurora González-Fierro
  • Erick de la Cruz-Hernandez
  • Enrique Perez-Cardenas
  • Lucia Taja-Chayeb
  • Daymi Arias-Bofill
  • Myrna Candelaria
  • Silvia Vidal
  • Alfonso Dueñas-GonzálezEmail author
Original Paper

Abstract

The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1–22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

Keywords

Epigenetic therapy Advanced cervical cancer Randomized phase III 

Notes

Acknowledgments

This work was supported by CONACyT grant AVANCE C01-294, and by Psicofarma, S.A. de C.V., Mexico. Sponsors did not participate in study design; collection, analysis, and interpretation of data; writing of the paper; nor decision to submit it for publication.

Conflict of interests

The authors have declared that no competing interests exist.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jaime Coronel
    • 1
  • Lucely Cetina
    • 1
  • Irlanda Pacheco
    • 3
  • Catalina Trejo-Becerril
    • 2
  • Aurora González-Fierro
    • 2
  • Erick de la Cruz-Hernandez
    • 2
  • Enrique Perez-Cardenas
    • 2
  • Lucia Taja-Chayeb
    • 2
  • Daymi Arias-Bofill
    • 1
  • Myrna Candelaria
    • 1
  • Silvia Vidal
    • 1
  • Alfonso Dueñas-González
    • 4
    Email author
  1. 1.Division of Clinical ResearchInstituto Nacional de Cancerología (INCan)Mexico CityMexico
  2. 2.Division de Basic ResearchInstituto Nacional de Cancerología (INCan)Mexico CityMexico
  3. 3.Department of RadiologyInstituto Nacional de Cancerología (INCan)Mexico CityMexico
  4. 4.Unit of Biomedical Research on Cancer (UBRC), Instituto de Investigaciones Biomédicas (IIB)Universidad Nacional Autonóma de Mexico (UNAM), Instituto Nacional de CancerologiaMexico CityMexico

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