title: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma.
abstract: PURPOSE Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. PATIENTS AND METHODS The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. CONCLUSION The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.
authors.affiliation: Departmentof Health and Human Services, Center for Cancer Researchand Cancer Therapy EvaluationProgram, National Cancer Institute,National Institutes of Health, Bethesda, USA. rpiekarz@nih.gov
authors.forename: Richard L
authors.initials: RL
authors.lastname: Piekarz
authors.forename: Robin
authors.initials: R
authors.lastname: Frye
authors.forename: Maria
authors.initials: M
authors.lastname: Turner
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kirschbaum
authors.forename: Jasmine
authors.initials: J
authors.lastname: Zain
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Larisa J
authors.initials: LJ
authors.lastname: Geskin
authors.forename: Craig
authors.initials: C
authors.lastname: Reeder
authors.forename: David
authors.initials: D
authors.lastname: Joske
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Erin R
authors.initials: ER
authors.lastname: Gardner
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Stephen
authors.initials: S
authors.lastname: Lade
authors.forename: A Tito
authors.initials: AT
authors.lastname: Fojo
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D047630:Depsipeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin