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Updated: Aug 14, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A phase I clinical trial evaluating imatinib mesylate (Gleevec) in tumor-bearing cats
Joshua L Lachowicz1, Gerald S Post, Edwin Brodsky
1Veterinary Oncology and Hematology Center, 178 Connecticut Avenue, Norwalk, CT 06854, USA. jlachowicz@oncovet.com
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.
Insights
Oral imatinib mesylate showed minimal toxicity in tumor-bearing cats during a phase I trial. Further evaluation of this tyrosine kinase inhibitor is ongoing at 10 mg/kg for veterinary cancer treatment.
Area of Science:
- Veterinary Oncology
- Pharmacology
- Clinical Toxicology
Background:
- Imatinib mesylate is a tyrosine kinase inhibitor targeting overexpressed proteins in malignancies.
- Feline cancers like fibrosarcoma, squamous cell carcinoma, and mast cell tumors present treatment challenges.
- Previous treatments in cats included surgery, radiation, and chemotherapy.
Purpose of the Study:
- To evaluate the toxicity and determine a safe dosage of orally-administered imatinib mesylate in cats with cancer.
- To assess the safety profile of imatinib mesylate in a feline model.
Main Methods:
- A phase I clinical trial involving 9 tumor-bearing cats with various diagnoses.
- Administration of imatinib mesylate via oral route (PO) every 24 hours (q24h) with dose escalations.
- Toxicity assessment using complete blood count (CBC) and serum biochemistry, with additional diagnostics in some cases.
Main Results:
- Eight out of nine cats showed no significant toxicity.
- Minimal gastrointestinal toxicity was observed in one cat.
- The study identified a well-tolerated dosage range for imatinib mesylate in cats.
Conclusions:
- Oral imatinib mesylate demonstrates a favorable safety profile in tumor-bearing cats.
- Further investigation of imatinib mesylate at 10 mg/kg PO q24h is warranted for feline cancer therapy.
- Imatinib mesylate shows potential as a treatment option for various feline malignancies.
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