Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas

Toshihisa Hamada, Makoto Sugaya, Yoshiki Tokura, Mikio Ohtsuka, Ryoji Tsuboi, Tetsuo Nagatani, Mamori Tani, Mitsuru Setoyama, Shigeto Matsushita, Kazuhiro Kawai, Kentaro Yonekura, Tsuyoshi Yoshida, Toshiaki Saida, Keiji Iwatsuki

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11 Citations (Scopus)

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/m2 for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m2 in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m2 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/m2: two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m2 bexarotene. 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/m2 once daily and effective in Japanese patients with CTCL.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalJournal of Dermatology
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Keywords

  • bexarotene
  • clinical trial
  • cutaneous T-cell lymphoma
  • mycosis fungoides
  • retinoid X receptor

ASJC Scopus subject areas

  • Dermatology

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    Hamada, T., Sugaya, M., Tokura, Y., Ohtsuka, M., Tsuboi, R., Nagatani, T., Tani, M., Setoyama, M., Matsushita, S., Kawai, K., Yonekura, K., Yoshida, T., Saida, T., & Iwatsuki, K. (2017). Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas. Journal of Dermatology, 44(2), 135-142. https://doi.org/10.1111/1346-8138.13542