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/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.