A Phase I Clinical Trial Evaluating Imatinib Mesylate (Gleevec) in Tumor-Bearing Cats

Abstract

A phase I clinical trial evaluating the toxicity of orally-administered imatinib mesylate was performed in 9 tumor-bearing cats. Imatinib is a small molecule, tyrosine kinase inhibitor, which selectively blocks the function of overexpressed proteins associated with various malignancies. Cats included in the study had diagnoses of fibrosarcoma, squamous cell carcinoma, and mast cell tumor, and each cat was staged using CBC and serum biochemistry; urinalysis, thoracic radiographs, and abdominal ultrasonography were performed in some cats. Most cats were treated previously by surgery, radiation therapy, chemotherapy, or some combination of these treatments. None of the cats received any concurrent chemotherapy. Six cats were treated with imatinib mesylate at 1-2 mg/kg PO q24h. Dose escalations were made to 2, 4, and 10 mg/kg PO q24h in 5 cats. Two cats started therapy at 10 mg/kg PO q24h, and 1 cat started therapy at 15 mg/kg PO q24h; all 3 cats remained at these dosages. No signs of toxicity, as evaluated by CBC and serum biochemistry, were noted in 8 of the 9 cats, and minimal gastrointestinal toxicity was observed. Due to the low frequency of adverse effects, further evaluation of imatinib is ongoing at a dosage of 10 mg/kg PO q24h.

Clinicopathological Features and Outcome for Dogs with Mast Cell Tumors and Bone Marrow Involvement

“…Imatinib f was administered at the dosage of 4.4 mg/kg PO q24h at the 1st morning meal. In cats, imatinib mesylate has been administered at dosages ranging from 5 to 10 mg/kg, 34 but similar information is not available for dogs. According to preclinical toxicology studies in dogs, imatinib administered PO at dosages ≥10 mg/kg was associated with gastrointestinal, hepatic, and hematologic toxicity, whereas a dosage of 3 mg/kg appeared to be safe 37 .…”

“…Imatinib directly inhibits the catalytic activity of KIT by interfering with the binding of adenosine triphosphate, thereby blocking TK phosphorylation and downstream signaling 32 . Until now, few studies have investigated the efficacy of imatinib for treatment of MCTs in veterinary medicine, and most studies have been performed in cats or with canine cell culture lines 31,33–35 . The optimal drug dosage and duration of treatment await investigation in dogs.…”

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats

“…This toxicity resolved with dose reduction . In a phase I clinical trial of imatinib in tumour‐bearing cats no haematologic or biochemical toxicities were seen, and GI side effects were minimal . Toceranib has been used anecdotally in cats.…”

Clinical outcome,PDGFRβandKITexpression in feline histiocytic disorders: a multicentre study

“…However, both veterinary TKIs target KIT and it is important to determine if the anecdotal responses to these drugs are because of the activity against this target. Imatinib and masitinib have been showing some efficacy against injection‐site sarcomas cells in vitro and phase I trials have proved safety for these drugs to be used in the feline species . No measurable responses in vivo to TKIs have been reported in cats with histiocytic disease so far.…”