Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies

Abstract

These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.

A phase II multiple dose clinical trial of histone deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple myeloma

“…Phase I-II clinical trials are underway or have been recently performed with SAHA in patients with advanced hematological malignancies, including MM [6][7][8][9][10][11][12][13]. Overall, these studies showed that SAHA was tolerable, although its toxicity profile was not negligible.…”

“…Not unexpectedly, patients treated with SAHA for hematological malignancies experienced more grade 3-4 hematological toxicity than patients with solid tumors [6,14]. Thrombocytopenia occurring with SAHA was associated with the presence of hypolobular megakaryocytes, and not with an absolute reduction in the number of megakaryocytes [7]. This may raise the possibility that SAHA impairs megakaryocyte differentiation.…”

“…One class of HDACIs is the hydroxamate derivatives family of compounds whose prototype is suberoyl anilide hydroxamic acid (SAHA) [5], which is being tested clinically in several hematological malignancies and has obtained FDA approval for the treatment of cutaneous T-cell lymphoma [6][7][8][9][10][11][12][13][14][15]. Our group has recently reported that ITF2357, an orally effective member of the family of hydroxamate-derived HDACIs, is a potent inducer of apoptosis and death of MM cells in vitro [16].…”

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

“…Vorinostat, a class I and II HDAC inhibitor, was approved more than 10 years ago for the treatment of CTCL [159]. Romidepsin, a pan-HDAC inhibitor, is also approved for use in CTCL patients as well as for relapsed and refractory PTCL.…”

Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy

“…64,[80][81][82] Also, Vorinostat and other HDIs have exhibited encouraging anti-cancer activity and relatively low patient toxicity in early clinical trials. [83][84][85][86][87][88][89] As a result, in October 2006, Vorinostat was approved by the FDA for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have tried and failed other therapies (www.fda.gov/cder/Offices/OODP/whatsnew/ vorinostat.htm). Presumably, the encouraging clinical activity of Vorinostat is, at least in part, due to its preferential killing of transformed cells compared to primary cells.…”