A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers
Varun MongaMohammed Milhem

Abstract

Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients >18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m² (day 1, day 8), and docetaxel 75 mg/m² (day 8). Cycles were of 28 day durat...Continue Reading

References

Nov 18, 1971·The New England Journal of Medicine·J Folkman
Jan 18, 1996·The New England Journal of Medicine·M J Brodie, M A Dichter
Jan 1, 1997·Journal of Cancer Research and Clinical Oncology·R Schneider-StockA Roessner
Apr 27, 2000·Journal of Cancer Research and Clinical Oncology·C KuhnenK M Müller
May 29, 2000·Journal of Cellular Physiology·W D Cress, E Seto
Jul 5, 2001·Cellular and Molecular Life Sciences : CMLS·S TimmermannA Harel-Bellan
Mar 29, 2002·The Prostate·Xu-Bao ShiRalph W deVere White
Aug 2, 2003·The New England Journal of Medicine·James C YangSteven A Rosenberg
Feb 24, 2004·Molecular Pharmacology·Martin MichaelisJindrich Cinatl
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Sep 30, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David R D'AdamoRobert G Maki
Oct 6, 2005·Cancer Research·Jens M TeodoridisRobert Brown
Jan 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David Z QianRoberto Pili
Feb 24, 2006·British Journal of Cancer·R M GlasspoolR Brown
Dec 15, 2006·The New England Journal of Medicine·Alan SandlerDavid H Johnson
Sep 1, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M CandelariaA Dueñas-González
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Henry S FriedmanTimothy Cloughesy
Jul 13, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C F VerschraegenT Bocklage
Aug 23, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M AgulnikR S Benjamin
Sep 26, 2013·International Journal of Molecular Sciences·Pavla BrachovaKimberly K Leslie
Mar 22, 2014·Cancer Cell·Patricia A J Muller, Karen H Vousden
Feb 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martee L HensleyHelen Michael
Dec 10, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K KoehlerJ L Chen
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C F VerschraegenT Bocklage

❮ Previous
Next ❯

Citations

Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dahea YouLauren M Aleksunes
Jul 23, 2020·Molecular Diagnosis & Therapy·Aikaterini MastorakiEmmanouil Pikoulis
Jul 14, 2019·Clinical Epigenetics·Yorick JanssensBart De Spiegeleer
Jun 21, 2019·Medicinal Research Reviews·Daniela TomaselliAntonello Mai
Dec 3, 2020·Frontiers in Oncology·Donglu WuDa Liu
Dec 18, 2020·Frontiers in Oncology·Pierre-Yves CrenNicolas Penel
Apr 1, 2021·Medicine·Anastasios KyriazoglouMaria Gavriatopoulou

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation

Clinical Trials Mentioned

NCT01106872

Software Mentioned

SAS

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Carcinosarcoma

Carcinosarcoma is a malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. Discover the latest research on carcinosarcoma here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.