| Abstract: | Introduction: STI571 (Gleevec, imatinib mesylate) is a receptor tyrosine kinase inhibitor with selectivity for Bcr‐Abl, platelet‐derived growth factor (PDGF), stem cell factor (SCF), and c‐Kit. Side effects with use in humans include vomiting, diarrhea, nausea, myalgia, edema, and cutaneous reactions. Renal and hepatic toxicity have also been reported. In dogs, there is significant hepatic toxicity at sub‐clinical doses. The purpose of this prospective study was to determine the toxicity level and potential treatment protocol in tumor bearing cats. Methods: A phase I clinical trial was performed in client owned cats using an escalating dose of STI571 in tumor bearing cats. Cats included in the study had a histologic diagnosis of fibrosarcoma or other tumors and were staged with CBC, biochemical profile, thoracic radiographs, and abdominal ultrasound. None of the cats received concurrent chemotherapy, but those previously treated with surgery, radiation therapy, or chemotherapy, were not excluded. The initial starting dose was 5 mg/cat PO SID and was gradually increased to 10 and 20 mg/cat PO SID at a 2–6 week interval depending on laboratory work and disease progression. A repeat physical examination, CBC, and biochemical profile, were performed every 2 weeks for 2 rechecks, then every 4 weeks. Results: Six cats were enrolled in the study. Four cats had oral squamous cell carcinoma, and two cats had cutaneous fibrosarcoma. One cat demonstrated leukocytosis, increased liver enzymes, and signs of acute renal failure two weeks after initiating therapy (5 mg PO SID). No dose escalation was made in this cat. Five cats endured dose escalations of 10 mg PO SID in two cats and 20 mg PO SID in three cats and were treated for 2–4 months. None of these cats experienced any signs of toxicity as measured by CBC and biochemical profile. Conclusions: Only one cat experienced toxicity that may have been associated with low dose administration of STI571. As most cats tolerated the drug without an adverse effect, further evaluation of STI571 in a phase II clinical trial is warranted. |
