title: Phase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma.
abstract: A phase I study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of the oral histone deacetylase (HDAC) inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL). Six patients received vorinostat (400 mg p.o., once daily). Dose-limiting toxicities (DLT) were evaluated in all six patients during the 28 days of the first cycle. One of the six patients who received vorinostat developed a DLT (grade 4 thrombocytopenia). The most common drug-related adverse events included nausea (4/6, 67%), thrombocytopenia (4/6, 67%), hyperbilirubinemia (3/6, 50%) and vomiting (3/6, 50%). Most of these events were reversible and were resolved by supportive care and/or the interruption of vorinostat treatment. The safety and PK profiles of vorinostat in Japanese patients with CTCL did not appear to differ from those previously observed in non-Japanese and Japanese patients with advanced solid tumors. None of the patients achieved an objective response in this study. However, one unconfirmed partial response and two cases of sustained stable disease for 12 weeks or longer were observed among the six patients in the study. One of the three evaluable patients experienced pruritus relief. Vorinostat was well tolerated at a dose of 400 mg p.o. once daily and showed potential efficacy in Japanese patients with CTCL, warranting further investigation.
authors.affiliation: Department of Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Wada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Noguchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006932:Hyperbilirubinemia / Q000139:chemically induced; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat