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

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 .