title: Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas.
abstract: Safety, tolerability, pharmacokinetics and efficacy of bexarotene, a novel retinoid X receptor (RXR)-selective retinoid, were evaluated in Japanese patients with stage IIB-IVB and relapsed/refractory stage IB-IIA cutaneous T-cell lymphomas (CTCL). This study was conducted as a multicenter, open-label, historically controlled, single-arm phase I/II study. Bexarotene was p.o. administrated once daily at a dose of 300 mg/m2for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m2in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m2met the response criteria using the modified severity-weighted assessment tool (mSWAT) at 24 weeks or discontinuation. Dose-limiting toxic effects (DLT) were present in four of 13 patients (31%) at a dose of 300 mg/m2: two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m2bexarotene. In the 13 patients at 300 mg/m2, common drug-related adverse events (AE) included hypothyroidism (92%), hypercholesterolemia (77%), leukopenia or neutropenia (39%), nasopharyngitis or anemia (31%). The treatment-related grade 3 AE included hypertriglyceridemia (4/16 patients, 25%), increased alanine aminotransferase, increased aspartate aminotransferase, dyslipidaemia, leukopenia and neutropenia (1/16 patients, 6%), and one of 16 patients experienced grade 4 hypertriglyceridemia. No patients discontinued bexarotene due to the AE during the study, but dose reduction or suspension was required. Bexarotene was shown to be well tolerated at 300 mg/m2once daily and effective in Japanese patients with CTCL.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.affiliation: Department of Dermatology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.affiliation: Department of Dermatology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagatani
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mamori
authors.initials: M
authors.lastname: Tani
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Setoyama
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazuhiro
authors.identifier: http://orcid.org/0000-0001-9375-0713
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Dermatology, Imamura Bun-in Hospital, Kagoshima, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yonekura
authors.affiliation: Minophagen Pharmaceutical, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Dermatology, Shinshu University, Nagano, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077610:Bexarotene; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047488:Retinoid X Receptors / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D016588:Anticarcinogenic Agents; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene
keywords: bexarotene; clinical trial; cutaneous T-cell lymphoma; mycosis fungoides; retinoid X receptor