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Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T‐cell lymphomas
Author(s) -
Hamada Toshihisa,
Sugaya Makoto,
Tokura Yoshiki,
Ohtsuka Mikio,
Tsuboi Ryoji,
Nagatani Tetsuo,
Tani Mamori,
Setoyama Mitsuru,
Matsushita Shigeto,
Kawai Kazuhiro,
Yonekura Kentaro,
Yoshida Tsuyoshi,
Saida Toshiaki,
Iwatsuki Keiji
Publication year - 2017
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.13542
Subject(s) - bexarotene , tolerability , leukopenia , medicine , neutropenia , gastroenterology , hypertriglyceridemia , adverse effect , anemia , pharmacology , retinoid x receptor , chemotherapy , cholesterol , triglyceride , chemistry , biochemistry , nuclear receptor , transcription factor , gene
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/m 2 for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m 2 in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m 2 met 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/m 2 : two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m 2 bexarotene. In the 13 patients at 300 mg/m 2 , 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/m 2 once daily and effective in Japanese patients with CTCL .