Neurology

Research Abstract

N08 - Microsurgery and intratumoral Concentration and Safety of Metronomic Chlorambucil for Spontaneous Canine Glioma

Thursday, June 14
12:00 PM - 12:15 PM
Location: WSCC 606/607

Investigate the distribution and safety of metronomic (daily low-dose) 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 q 24hr for ≥ 3 days, and continued postoperatively until death or dose-limiting adverse events. The chlorambucil concentration of 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.


Seven oligodendrogliomas and 1 astrocytoma (6 high-grade, 2 low-grade) underwent complete microsurgical resection. Median surgical glioma specimen chlorambucil concentration was 0.52 ng / g (range, 0 – 2.62 ng / g), or 37% (range, 0–178%) of the serum concentration. Median cerebrospinal fluid concentration was 0.1 ng / mL (range, 0–0.3 ng / mL). Chlorambucil was not associated with an increase in seizure activity. Six dogs displayed prolonged seizure-free intervals. There was no myoclonus. Three dogs developed asymptomatic thrombocytopenia after 8 to 12 months of chlorambucil. Median progression-free survival was 253 days (range, 63 – 860 days). Median overall survival was 257 days (range, 64–860 days).  


The presence of intratumoral chlorambucil indicated an altered blood brain barrier that varied from case to case. Despite sporadic previous reports of neurotoxicity, prolonged seizure-free intervals supported a high safety margin at this dose in this species. Metronomic chlorambucil was well tolerated.

R. Timothy Bentley, BVSc (Dist), MRCVS, DACVIM (Neurology)

Associate Professor, Veterinary Neurology
Veterinary Clinical Sciences, Purdue University

Liverpool University BVSc (Dist) 2005. Member of the Royal College of Veterinary Surgeons 2005. DACVIM (Neurology) 2009.
Rotating Small Animal Internship, Royal Veterinary College, University of London, 2005 - 2006.
Veterinary Neurology & Neurosurgery Residency, Tufts University, 2006 - 2009.
Purdue University, Veterinary Neurology & Neurosurgery: Assistant Professor (2009 - 2016), Associate Professor (2016 - Present).
At Purdue University, runs a multi-disciplinary brain tumor research program with focus upon canine glioma as a model for human glioma. Other research interests include developing application of MRI.

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