Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors

Abstract

Romidepsin is a histone deacetylase inhibitor (HDI), approved by the US FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Although various mechanisms have been proposed for the activity of HDIs, including induction of genes controlling cell cycle, acetylation of cytoplasmic proteins and direct induction of apoptosis, the mechanism underlying activity of romidepsin and other HDIs in CTCL is not known. Romidepsin induces long-lasting responses. The side-effect profile is similar to that of other HDIs, causing fatigue, nausea and thrombocytopenia. Management of the CTCL population requires vigilence to prevent infection with skin contaminants, and monitoring of potassium and magnesium, electrolytes found to be low in a large proportion of patients. Electrocardiographic (ECG) changes are common but are not associated with myocardial damage. When molecular end points were evaluated in 61 patients enrolled on a Phase II trial with romidepsin, response was associated with persistence of acetylated histone H3, suggesting that drug exposure is important in effective therapy with romidepsin. Future studies will endeavor to identify combination strategies to increase the efficacy both in resistant CTCL and in solid tumors and to identify biomarkers of response that will allow selection of patients most likely to benefit from the therapy.

3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

“…A phase I clinical trial showed JNJ-26481585 to have a much greater plasma half-life of 8.8 hours in patients with advanced solid tumors compared to other HDAC inhibitors, such as vorinostat and romidepsin (49,50), and it shows promise for use in solid tumors either as a single agent or in combination with SOC (35). The dismal plight of those with advanced NSCLC and the observation here that even early-stage tumors are insensitive to current SOCs highlights the need for novel therapeutic or combinatorial options in this setting.…”

Untitled

“…SAHA (vorinostat) was approved by the US Food and Drug Administration for the treatment of cutaneous T-cell lymphoma in 2006 [45], as was romidepsin (FK228) in 2009 [57]. Both Mocetinostat (MGCD 0103) and Entinostat (MS-275) are currently undergoing clinical trials for the treatment of various cancer types, including lymphomas and solid tumors [44,58,59].…”

Controversies Surrounding the Potential Use of Histone Deacetylase Inhibitors for the Treatment of Asthma

“…This provides the basis of their clinical utility in cancer. Indeed, suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) and the cyclic peptide, depsipeptide (Romidepsin, Istodax), have been approved by the US FDA, for the treatment of cutaneous T-cell lymphoma [102][103][104][105].…”