Canine (Pet Dog) Tumor Microsurgery and Intratumoral Concentration and Safety of Metronomic Chlorambucil for Spontaneous Glioma: A Phase I Clinical Trial

World Neurosurgery
R Timothy BentleyAaron A Cohen-Gadol

Abstract

Metronomic (daily low-dose) chlorambucil requires further study before use in human patients with glioma. The aim of this study was to investigate distribution and safety of metronomic chlorambucil in naturally occurring canine glioma. Eight client-owned (pet) dogs with newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil was administered preoperatively at 4 mg/m2 every 24 hours for ≥3 days and continued postoperatively until death or dose-limiting adverse events. Chlorambucil concentrations in the surgical glioma specimen, cerebrospinal fluid, and serum were analyzed. Dogs additionally received lomustine postoperatively. Dogs were monitored for seizures, myoclonus, cytopenias, and tumor recurrence. Complete microsurgical resection was achieved in 7 oligodendrogliomas and 1 astrocytoma (6 high grade, 2 low grade). Median surgical glioma specimen chlorambucil concentration was 0.52 ng/g (range, 0-2.62 ng/g), or 37% (range, 0%-178%) of serum concentration. Median cerebrospinal fluid concentration was 0.1 ng/mL (range, 0-0.3 ng/mL). Chlorambucil was not associated with increase in seizure activity. Six dogs displayed prolonged seizure-free intervals. There was no myoclonus. Three dogs developed asymptomatic...Continue Reading

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Citations

Mar 17, 2020·Expert Opinion on Drug Discovery·Michael D Lucroy, Mark A Suckow
May 21, 2021·Frontiers in Veterinary Science·R Timothy BentleyJohn H Rossmeisl
Jun 13, 2021·Journal of Veterinary Internal Medicine·Roberto José-LópezMartí Pumarola
Aug 27, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·C Elizabeth BoudreauAmy B Heimberger

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