Repeat radiation with bevacizumab and minocycline in bevacizumab-refractory high grade gliomas: a prospective phase 1 trial

Introduction There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety a...

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Published in:Journal of neuro-oncology 2020-07, Vol.148 (3), p.577-585
Main Authors: Cohen, Adam L., Anker, Christopher J., Johnson, Brett, Burt, Lindsay M., Shrieve, Dennis C., Salzman, Karen, Jensen, Randy, Boucher, Ken, Colman, Howard
Format: Article
Language:English
Subjects:
Antibiotics
Bevacizumab
Clinical Study
Cognition
Dosage
Glioma
Immunotherapy
Medicine
Medicine & Public Health
Microglia
Minocycline
Monoclonal antibodies
Neurology
Oncology
Survival
Targeted cancer therapy
Temozolomide
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Summary:Introduction There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. Methods The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. Results The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. Conclusions Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-020-03551-3