Abstract
BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m(2) daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m(2) day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m(2) day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.