Phase 1 and 2 Trial of Bexarotene Gel for Skin-Directed Treatment of Patients With Cutaneous T-Cell Lymphoma

Objective To evaluate the safety, dose tolerance, and efficacy of topical bexarotene gel in patients with early-stage cutaneous T-cell lymphoma (CTCL). Design Phase 1 and 2, open-label, dose-escalation clinical trial of bexarotene gel. Setting Three university-based clinics. Participants Sixty-seven adults with early-stage (TNM stages IA-IIA) CTCL. Interventions Bexarotene gel, 0.1%, 0.5%, and 1.0%, applied in incremental dose adjustments from 0.1% gel every day to 1.0% gel 4 times daily or the maximal tolerated dose. Main Outcome Measures Patients were followed for efficacy and safety, and treatment continued as long as they benefited. Response (≥50% improvement) was evaluated by the Physician's Global Assessment of cutaneous disease and by an overall severity assessment of cutaneous disease, including signs of CTCL and area involved. Results Most patients tolerated topical bexarotene at 1% gel twice daily for routine use. Adverse events were generally mild to moderate in severity and were confined to treatment sites. Treatment-limiting toxic effects were associated with skin irritation and increased with gel exposure. Patients achieved an overall response rate of 63% and a clinical complete response rate of 21%. Median projected time to onset of response was 20.1 weeks (range, 4.0-86.0 weeks), and the estimated median response duration from the start of therapy was 99 weeks. Patients with no previous therapy for mycosis fungoides responded at a higher rate (75%) than those who previously underwent topical therapies (67%). Conclusions Bexarotene gel was well tolerated, was easily self-applied, and had a substantial response rate in treating patients with early-stage CTCL.