Reverse swing‐M, phase 1 study of repurposing mebendazole in recurrent high‐grade glioma

Autor: Abhishek Mahajan, Ram Abhinav, Ameya D Puranik, Amit Janu, Vijay Patil, Nandini Menon, Nilendu Purandare, Tejpal Gupta, Epari Sridhar, Rakesh Jalali, Arti Bhelekar, Ankita Ahuja, Vijai Simha, Anuja Abhyankar, Rahul Krishnatry, Atanu Bhattacharjee
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Gastroenterology
0302 clinical medicine
Lomustine
Recurrence
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
Original Research
Brain Neoplasms
Checkpoint
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Ondansetron
Mebendazole
Oncology
030220 oncology & carcinogenesis
Salvage
High‐grade Glioma
Female
medicine.symptom
Repurposing
medicine.drug
Adult
medicine.medical_specialty
Maximum Tolerated Dose
Nausea
Anemia
Antineoplastic Agents
lcsh:RC254-282
Medication Adherence
Re-Irradiation
03 medical and health sciences
Internal medicine
Glioma
medicine
Temozolomide
Humans
Radiology
Nuclear Medicine and imaging
Adverse effect
High-Grade Glioma
Aged
Salvage Therapy
business.industry
Drug Repositioning
Clinical Cancer Research
medicine.disease
030104 developmental biology
Antiemetics
Neoplasm Recurrence
Local
business
Glioblastoma
Zdroj: Cancer Medicine, Vol 9, Iss 13, Pp 4676-4685 (2020)
Cancer Medicine
ISSN: 2045-7634
Popis: 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/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 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.
This was a phase 1 study in relapsed recurrent glioma for repurposing Mebendazole. The recommended dose identified for future studies for mebendazole in adult glioma patients was 4800 mg per day with both temozolomide‐radiation and single‐agent temozolomide while it was 2400 mg with CCNU.
Databáze: OpenAIRE
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