Bicyclic depsipeptide, a histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T cell lymphoma who have received at least one prior systemic treatment.
Catalyzes the removal of acetyl groups from acelytated lysine residues in histones, resulting in the modulation of gene expression.
Trade name ISTODAX.
Dose of 14 mg/m2 as 4 hour infusion on days 1,8, and 15 every 28 days.
Extensively metabolized by cytochrome P450 CYP3A4 which can lead to many drug interactions.
High incidence of nausea and vomiting in up to 86% of patients (Piekarz RL).
Use of antiemetics strongly suggested.
The most common grade 3/4 adverse reactions were infections (11%) and asthenia/fatigue (8%), lymphopenia (37%), neutropenia (27%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).
May be associated with myelosuppression and in increase in serious and fatal infections including pneumonia, sepsis, and viral reactivation.
In a study of single agent romidepsin in patients with relapsed or refractory PTCL had an overall response rate of 38%, median duration of response of 8.9 months (Piekarz RL et al).
Agents that prolong QTc interval or agents that inhibit CYP3A4 are to be avoided.
ECG changes observed in patients with general long QT syndrome, patients with antiarrhythmic medications that lead to QT prolongation.
Tumor lysis syndrome has been reported
Avoided in pregnancy.
In a phase 2 study in progressive or relapsed peripheral T-cell lymphoma following prior systemic therapy 131 patients with a mean age of 59.4 years and the median time since diagnosis of 1.25 years receiving 14 mg for meter squared by four hour infusion on days one, eight, and 15 of the 28 day cycle for up to six cycles: 26% response rate, with CR and 13% and 13% with PR (Coiffer B et al).
Recommended dose 14 mg/m² intravenously over 4 hours days 1, 8, and 15 of a a 28 day cycle-repeated monthly.