Abstract | PURPOSE: EXPERIMENTAL DESIGN: This was a Phase I trial in which successive cohorts of dogs with spontaneous tumors that had failed standard treatment regimens received escalating doses of SU11654 as oral therapy. Pharmacokinetics, toxicity, and tumor response were assessed. RESULTS: Fifty-seven dogs with a variety of cancers were enrolled; of these, 10 experienced progressive disease within the first 3 weeks. Measurable objective responses were observed in 16 dogs (including 6 complete responses), primarily in mast cell tumors (n = 11), mixed mammary carcinomas (n = 2), soft tissue sarcomas (n = 2), and multiple myeloma (n = 1), for an overall response rate of 28% (16 of 57). Stable disease of sufficient duration to be considered clinically meaningful (>10 weeks) was seen in an additional 15 dogs, for a resultant overall biological activity of 54% (31 of 57). CONCLUSIONS: This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies. Given the similarities of canine and human cancers with regard to tumor biology and the presence of analogous RTK dysregulation, it is likely that such agents will demonstrate comparable antineoplastic activity in people.
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Authors | Cheryl A London, Alison L Hannah, Regina Zadovoskaya, May B Chien, Cynthia Kollias-Baker, Mona Rosenberg, Sue Downing, Gerald Post, Joseph Boucher, Narmada Shenoy, Dirk B Mendel, Gerald McMahon, Julie M Cherrington |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 9
Issue 7
Pg. 2755-68
(Jul 2003)
ISSN: 1078-0432 [Print] United States |
PMID | 12855656
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Enzyme Inhibitors
- Indoles
- Pyrroles
- toceranib phosphate
- Proto-Oncogene Proteins c-kit
- Receptor Protein-Tyrosine Kinases
- Receptors, Vascular Endothelial Growth Factor
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Dog Diseases
(drug therapy)
- Dogs
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- Female
- Indoles
(administration & dosage, therapeutic use)
- Inhibitory Concentration 50
- Male
- Models, Chemical
- Mutation
- Neoplasms
(drug therapy, veterinary)
- Proto-Oncogene Proteins c-kit
(genetics)
- Pyrroles
(administration & dosage, therapeutic use)
- Receptor Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Receptors, Vascular Endothelial Growth Factor
(metabolism)
- Time Factors
- Tomography, X-Ray Computed
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