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Peer-reviewed veterinary case report

Safety and brain tumor drug levels in dogs given daily low-dose

By Bentley, R Timothy et al.·Published in World neurosurgery·2018·Department of Veterinary Clinical Sciences, United States·View original on PubMed

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

Species:
dog

Plain-English summary

An 8-year-old mixed-breed dog was diagnosed with a brain tumor called glioma and underwent surgery to remove it. Before and after the surgery, the dog was given a low-dose chemotherapy drug called chlorambucil to see how well it worked and if it was safe. The treatment did not increase seizure activity, and in fact, six dogs had longer periods without seizures. Most dogs lived for about 257 days after treatment, and the drug was generally well tolerated, with only a few experiencing mild side effects.

People also search for: dog brain tumor treatment · glioma in dogs · chlorambucil for dogs · dog seizures after surgery · dog cancer survival rates

Abstract

OBJECTIVE: 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. METHODS: Eight client-owned (pet) dogs with newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil was administered preoperatively at 4 mg/mevery 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. RESULTS: 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 thrombocytopenia after 8-12 months of chlorambucil. Median progression-free survival was 253 days (range, 63-860 days). Median overall survival was 257 days (range, 64-860 days). CONCLUSIONS: 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. Spontaneous canine glioma offers a robust preclinical model.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/29775768/