Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors.
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.
Grant
Cliona
C
Medical Oncology Branch, SAIC-Frederick, NCI-Frederick, MA, USA.
Rahman
Fahd
F
Piekarz
Richard
R
Peer
Cody
C
Frye
Robin
R
Robey
Robert W
RW
Gardner
Erin R
ER
Figg
William D
WD
Bates
Susan E
SE
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D017322:Clinical Trials, Phase II as Topic; D047630:Depsipeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005221:Fatigue / Q000139:chemically induced; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018390:Gene Targeting; D006331:Heart Diseases / Q000139:chemically induced; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D007239:Infections / Q000209:etiology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D017410:Practice Guidelines as Topic
D000970:Antineoplastic Agents; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; C087123:romidepsin; D006655:Histone Deacetylases