Open AccessJournal Article
Phase I Dose-Escalating Study of SU11654, a Small Molecule Receptor Tyrosine Kinase Inhibitor, in Dogs with Spontaneous Malignancies,
Cheryl A. London,Alison L. Hannah,Regina Zadovoskaya,May B. Chien,Cynthia Kollias-Baker,Mona P. Rosenberg,Sue Downing,G. S. Post,Joseph F. Boucher,Narmada Shenoy,Dirk B. Mendel,Gerald McMahon,Julie M. Cherrington +12 more
TLDR
This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies in dogs, and it is likely that such agents will demonstrate comparable antineoplastic activity in people.Abstract:
Purpose : The purpose of the following study was to investigate the safety and efficacy of the novel multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor, SU11654, using a canine model of spontaneous tumors. This p.o. bioavailable compound exhibits potent inhibitory activity against members of the split kinase family of RTKs, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Kit, and Flt-3, resulting in both direct antitumor and antiangiogenic activity. 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.read more
Citations
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Translation of new cancer treatments from pet dogs to humans.
Melissa Paoloni,Chand Khanna +1 more
TL;DR: Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone, and has been increasingly recognized in the field of cancer research.
Journal ArticleDOI
Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision
Cheryl A. London,Phyllis B. Malpas,Stacey L. Wood-Follis,Joseph F. Boucher,Anthony Rusk,Mona P. Rosenberg,Carolyn J. Henry,Kathy L. Mitchener,Mary K. Klein,John G. Hintermeister,Philip J. Bergman,Guillermo Couto,Guy N. Mauldin,Gina M. Michels +13 more
TL;DR: Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine planned treatment breaks, and shows that spontaneous tumors in dogs are good models to evaluate therapeutic index of targeted therapeutics in a clinical setting.
Journal ArticleDOI
Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors
Kevin A. Hahn,Gregory K. Ogilvie,Rusk T,Devauchelle P,Amy K. LeBlanc,Alfred M. Legendre,Barbara E. Powers,Phillip S. Leventhal,Jean-Pierre Kinet,Fabienne Palmerini,Patrice Dubreuil,Alain Moussy,Olivier Hermine +12 more
TL;DR: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.
Journal ArticleDOI
Canine tumors: a spontaneous animal model of human carcinogenesis.
Salomé S. Pinho,Salomé S. Pinho,Sandra Carvalho,Joana I.T.A. Cabral,Celso A. Reis,Celso A. Reis,Fátima Gärtner,Fátima Gärtner +7 more
TL;DR: The importance of naturally occurring canine tumors as valuable tools for studying numerous aspects of human cancer as well as the potential use of this animal model for the development of new cancer treatments are summarized.
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TL;DR: Sequencing of c-kit complementary DNA from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains, suggesting that the mutations contribute to tumor development.
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New guidelines to evaluate the response to treatment in solid tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
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