Phase II study of the histone-deacetylase inhibitor ITF2357 in relapsed/refractory Hodgkin’s lymphoma patients

Viviani, Simonetta; Bonfante, V.; Fasola, Cinzia; Valagussa, Pinuccia; Gianni, A. M.

doi:10.1200/jco.2008.26.15_suppl.8532

Cited by 13 publications

(9 citation statements)

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“…ITF2357 has been investigated in Phase II clinical trials for the treatment of MM [Galli et al, ] and Hodgkin's lymphoma [Viviani et al, ]. Although ITF2357 was generally well tolerated, only 6/15 myeloma patients achieved SD [Galli et al, ] and 7 of 13 lymphoma patients achieved SD [Viviani et al, ].…”

Section: Hdacis Alter Mirna Expression In a Range Of Cancersmentioning

confidence: 99%

Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review

Ali

Humphreys

Michael

2015

Drug Development Research

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Chromatin-modifying drugs, such as histone deacetylase inhibitors (HDACi), have shown potential as cancer therapeutics, either alone or in combination with other therapies. HDACi have the ability to reverse aberrant epigenetic modifications associated with cancer, namely dysregulated histone acetylation. There are currently three FDA approved HDACi; vorinostat, romidepsin, and panobinostat. Epigenetic modifications can regulate the expression of protein coding genes, and in addition can alter expression of microRNA (miRNA) genes. Many miRNAs play key roles in cell proliferation and apoptosis, and are commonly dysregulated in cancer states. A number of in vitro and in vivo studies have demonstrated the ability of chromatin-modifying drugs to alter miRNA expression, which may provide the basis for further investigation of miRNAs as therapeutic targets or as biomarkers of drug response. This review summarises findings from studies investigating the effects of HDACi on miRNA expression, as well as key clinical trials involving HDACi. Understanding how chromatin-modifying drugs epigenetically modulate miRNA genes provides further insight into the cellular mechanisms that deliver therapeutic responses, and may assist in refining treatment strategies.

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Section: Hdacis Alter Mirna Expression In a Range Of Cancersmentioning

confidence: 99%

Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review

Ali

Humphreys

Michael

2015

Drug Development Research

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“…In a phase II open-label nonrandomized clinical study involving heavily pretreated, relapsed, or refractory Hodgkin’s lymphoma patients, preliminary data showed that the oral application of ITF2375 had antitumor activity with an acceptable safety profile. The toxicity profile included grade 1 leukopenia in 30%, grade 2 thrombocytopenia in 33%, fatigue in 50%, grade 1 diarrhea in 40%, and cardiac QT persistence leading to drug discontinuation in 20% of treated patients 99. Mocetinostat (MGCD0103) is a novel HDACI that has strong isotype selectivity to HDAC1 and some weak inhibition to HDAC2, −3, and −11.…”

Section: Hdac Inhibitors In Clinical Trialsmentioning

confidence: 99%

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

Ververis¹,

Hiong²,

Karagiannis³

et al. 2013

BTT

138

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Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.

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“…A first oral one, gave stable diseases by computed tomography (CT) scan that have been associated with a significant reduction in fluorodeoxyglucose-positron emission tomography scan uptake. 149 Galli et al 150 developed a Phase II multicenter trial in 19 heavily treated patients that were relapsing from progressive multiple myeloma (MM) ( Table 3, AL). The best responses were disease stabilization.…”

Section: Givinostatmentioning

confidence: 99%

Interpreting clinical assays for histone deacetylase inhibitors

Bertrand¹,

Martinet²

2011

CMAR

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As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulation, epigenetic modifications participate in the malignant transformation of cells. Their reversible nature has led to the emergence of the promising field of epigenetic therapy. The efforts made to inhibit in particular the epigenetic enzyme family called histone deacetylases (HDACs) are described. HDAC inhibitors (HDACi) have been proposed as a viable clinical therapeutic approach for the treatment of leukemia and solid tumors, but also to a lesser degree for noncancerous diseases. Three epigenetic drugs are already arriving at the patient's bedside, and more than 100 clinical assays for HDACi are registered on the National Cancer Institute website. They explore the eventual additive benefits of combined therapies. In the context of the pleiotropic effects of HDAC isoforms, more specific HDACi and more informative screening tests are being developed for the benefit of the patients.

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Phase II study of the histone-deacetylase inhibitor ITF2357 in relapsed/refractory Hodgkin’s lymphoma patients

Cited by 13 publications

References 0 publications

Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review

Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

Interpreting clinical assays for histone deacetylase inhibitors

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