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Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Suberanilohydroxaxmic acid (SAHA; also known as Vorinostat) is a broad-spectrum HDAC inhibitor approved by the FDA in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who had progressive, persistent or recurrent disease on or following two systemic therapies (Duvic and Vu, 2007). Vorinostat is a linear hydroxamate compound, developed by Merck & Co. Inc. In addition to cutaneous T-cell lymphomas, SAHA was also tested against solid tumors such as the carcinomas of breast, head and neck, and Hodgkin’s lymphoma (Mottamal et al., 2015). Oral administration of SAHA (400 mg every day) produced an objective response of ~31% in a Phase II trial compared to an intermittent dosing, which yielded only 9% response (Pourrajab et al., 2020). However, severe side effects that include anemia and thrombocytopenia were reported in patients who had received Vorinostat by intravenous administration (Bubna, 2015). Vorinostat is currently being studied in 39 ongoing clinical trials as a monotherapeutic agent against leukemia, non–small cell lung cancer, multiple myelomas and breast, pelvic and prostate cancers (Siegel et al., 2009).
The Emerging Role of Histone Deacetylase Inhibitors in the Treatment of Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
SAHA, vorinostat, is the prototypical hyroxamate that has to date been extensively studied in the clinic and recently approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Vorinostat has the ability to induce differentiation and apoptosis in numerous cell lines, including erythroleukemia, bladder transitional cell carcinoma, breast adenocarcinoma, myeloma, and neuroblastoma (38) causing the accumulation of acetylated 2A, 2B, 3, and 4 histones (23). Phase I clinical trials showed that both IV and oral formulations were well tolerated in patients with both solid tumors and hematologic malignancies, including AML, NHL, Hodgkin’s lymphoma, and myeloma. In addition, promising signals of activity were appreciated in patients with Hodgkin’s lymphoma, T-cell lymphoma, and two patients with transformed lymphoma, [one CR for 10 months, one partial remission (PR) for 6 months].
Advances in Hodgkin’s lymphoma pharmacotherapy: a focus on histone deacetylase inhibitors
Published in Expert Opinion on Pharmacotherapy, 2023
Thuy Ho, Cara Coleman, Palak Shah, Victor Yazbeck
In an early phase 2 trial, vorinostat monotherapy showed modest activity in relapsed and refractory Hodgkin lymphoma. The Southwest Oncology Group (SWOG) S0517 phase II study [36] included 25 patients with R/R cHL who were previously treated with at least 5 lines of therapy, including autologous stem cell transplantation (ASCT). Patients received vorinostat 200 mg orally twice daily on a 2-weeks on and 1-week off schedule. The overall response rate (ORR) was only 4%, comprised of partial responses. There were no complete responses. Forty-eight percent of patients had stable disease, while 32% had progressive disease. Of note, there was inadequate data for evaluation in 16% of the patients. The median progression-free survival (PFS) was 4.8 months, and median overall survival (OS) was 15.7 months. Vorinostat was overall well-tolerated, with 28% incidence of grade 3 anemia, only 4% grade 4 anemia, 12% grade 3 lymphopenia, and 12% grade 4 thrombocytopenia. Therefore, single agent vorinostat cannot be used. However, improved responses were later observed with vorinostat-based combination regimens, which will be discussed in a later section.
Pharmacological treatment for transforming growth factor beta induced corneal dystrophies: what is the way forward?
Published in Expert Review of Clinical Pharmacology, 2023
Gabriella Guo Sciriha, Janet Sultana, Joseph Borg
Approved or investigational drugs that cause a decrease in TGFBI expression and/or promote TGFBIp degradation can be explored as a new cost-effective approach for the treatment of TGFBI CDs via drug repurposing [10]. Effective topical medications would be the solution to providing minimally invasive treatment to TGFBI CD patients in order to inhibit the deposition of corneal complexes as from the early stages, thus preventing symptoms and visual impairment. Lithium, doxycycline, nitric oxide and MMC are currently licensed for use in the treatment of various medical conditions by both the EMA and FDA. Vorinostat is also in the list of licensed drugs by the FDA. On the other hand, glucosamine and melatonin are widely available, as dietary supplements, both in the USA and in Europe. Currently, tranilast and givinostat are considered as orphan drugs by the EMA while vorinostat and halofuginone had also been granted orphan drug status in the past; however, this was withdrawn on request of the sponsor.
A drug safety evaluation of mogamulizumab for the treatment of cutaneous T-Cell lymphoma
Published in Expert Opinion on Drug Safety, 2019
Salma Afifi, Sara Mohamed, Jennifer Zhao, Francine Foss
Diarrhea and fatigue were generally mild and tolerable for mogamulizumab-treated patients and did not lead to any treatment discontinuations in the MAVORIC trial. On the contrary, fatigue was the most common reason for vorinostat treatment discontinuation, and diarrhea was the most common adverse event reported (62% all grade) with vorinostat. Other common adverse events reported in vorinostat-treated patients include nausea, thrombocytopenia, serum creatinine elevation, dysgeusia, and anorexia. Overall, mogamulizumab had a more tolerable side effect profile compared to vorinostat. This further translated into a significantly improved quality of life (QoL), as demonstrated by several QoL assessment scales, including Skindex-29 (p = 0.0002), FACT-G (p < 0.0001), 3-level EG-5D (p = 0.021), and ItchyQoL scale (p = 0.034). Furthermore, mogamulizumab has a relatively favorable adverse effect profile compared to other available treatment for CTCL (Table 2).