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

摘要: Objective Metronomic (daily low-dose) chlorambucil requires further study before use in human patients with glioma. The aim of this was to investigate distribution and safety metronomic naturally occurring canine Methods Eight client-owned (pet) dogs newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil administered preoperatively at 4 mg/m2 every 24 hours for ≥3 days continued postoperatively until death or dose-limiting adverse events. concentrations the surgical specimen, cerebrospinal fluid, serum analyzed. Dogs additionally received lomustine postoperatively. monitored seizures, myoclonus, cytopenias, tumor recurrence. Results Complete microsurgical resection achieved 7 oligodendrogliomas 1 astrocytoma (6 high grade, 2 low grade). Median specimen concentration 0.52 ng/g (range, 0–2.62 ng/g), 37% 0%–178%) concentration. fluid 0.1 ng/mL 0–0.3 ng/mL). not associated increase seizure activity. Six displayed prolonged seizure-free intervals. There no myoclonus. Three developed asymptomatic thrombocytopenia after 8–12 months chlorambucil. progression-free survival 253 63–860 days). overall 257 64–860 Conclusions presence intratumoral indicated an altered blood-brain barrier that varied from case case. Despite sporadic previous reports neurotoxicity, intervals supported a margin dose species. well tolerated. Spontaneous offers robust preclinical model.