Jankowski M¹, Fulton L², Sheafor S³, Prescott D², Khanna C.^1,4 - Friendship Hospital for Animals1, Washington D.C., VCA-Veterinary Referral Associates², Gaithersburg MD, SouthPaws Veterinary Specialists and Emergency Center³, Springfield VA, Pediatric Oncology Branch⁴, NCI-NIH, Bethesda MD.

INTRODUCTION
Angiogenesis is essential for cancer progression and metastasis. Inhibition of angiogenesis may be an effective treatment for cancers. The anticancer activity of thalidomide has been demonstrated in early human clinical trials. The objectives of this study are: 1) to determine the safety and efficacy of oral thalidomide against measurable canine cancers, 2) to define an optimal biological dose for thalidomide in dogs, and 3) to define tumor types sensitive to antiangiogenic therapy with thalidomide.

METHODS
This is a single agent, phase I/II clinical study. Entry requirements include measurable and histologically confirmed disease, body weight > 10 kg, no chemotherapy within 10 days of treatment, and informed owner consent. Three escalating dose cohorts (30 cases/cohort) have been defined: 3.3-6.5, 6.6-13, and 13.3-26 mg/kg QD. Physical examinations, CBC, serum biochemistry, and tumor response will be evaluated at day 0 and every 30 days thereafter. Urine and plasma samples collected before and during thalidomide therapy will be assayed for markers of antiangiogenic activity including, basic fibroblast growth factor, vascular endothelial growth factor and interleukin-8.

RESULTS
Six cases to date have been evaluated. All dogs had progressive disease prior to study entry. No side effects to thalidomide have been noted in the first dose cohort.

SD -Stable Disease; PD - Progressive Disease

DISCUSSION
Thalidomide appears be well tolerated in the current dose cohort. No objective tumor responses have been documented at this time. Additional entry of cases with smaller tumor burden may allow antiangiogenic activity to be exerted before disease progression. Surrogate markers of systemic antiangiogenic activity, measured in plasma and urine, may be helpful in defining optimal biologic dose.