Clinical and Immunomodulatory Effects of Toceranib Combined with Low-Dose Cyclophosphamide in Dogs with Cancer

Journal of Veterinary Internal Medicine

Volumn 26, Issue 2, 2012, Pages 355-362

  Mitchell, L ^a   Thamm, D H ^a   Biller, B J ^a  

^a Department of Environmental and Radiological Health Sciences   (United States)

Author keywords

Metronomic; Neoplasia; Regulatory T cell; Tyrosine kinase inhibitor

Indexed keywords

ALKYLATING AGENT; CYCLOPHOSPHAMIDE; GAMMA INTERFERON; IMMUNOLOGIC FACTOR; INDOLE DERIVATIVE; PYRROLE DERIVATIVE; TOCERANIB;

ANIMAL; ANIMAL DISEASE; ARTICLE; BLOOD; BLOOD CELL COUNT; CLINICAL TRIAL; DOG; DOG DISEASE; DRUG COMBINATION; DRUG EFFECT; FEMALE; FLOW CYTOMETRY; IMMUNOLOGY; MALE; NEOPLASM; PROSPECTIVE STUDY; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; BLOOD CELL COUNT; CYCLOPHOSPHAMIDE; DOG DISEASES; DOGS; DRUG THERAPY, COMBINATION; FEMALE; FLOW CYTOMETRY; IMMUNOLOGIC FACTORS; INDOLES; INTERFERON-GAMMA; MALE; NEOPLASMS; PROSPECTIVE STUDIES; PYRROLES; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

ANIMALIA; CANIS FAMILIARIS; MUS;

EID: 84858749413     PISSN: 08916640     EISSN: 19391676     Source Type: Journal    
DOI: 10.1111/j.1939-1676.2011.00883.x     Document Type: Article

References (34)

1. London CA, Hannah AL, Zadovoskaya R, et al. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003;9:2755-2768.
2. Arora A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 2005;315:971-979.
3. Shawver LK, Slamon D, Ullrich A. Smart drugs: Tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002;1:117-123.
4. Hynes NE, Lane HA. ERBB receptors and cancer: The complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341-354.
5. London CA, Malpas PB, Wood-Follis SL, et al. 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. Clin Cancer Res 2009;15:3856-3865.
6. Ozao-Choy J, Ma G, Kao J, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res 2009;69:2514-2522.
7. Finke JH, Rini B, Ireland J, et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 2008;14:6674-6682.
8. Yang Z, Zhang B, Li D, et al. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS ONE 2010;5:e8922.
9. Biller BJ, Guth A, Burton JH, et al. Decreased ratio of CD8 + T cells to regulatory T cells associated with decreased survival in dogs with osteosarcoma. J Vet Intern Med 2010;24:1118-1123.
10. Horiuchi Y, Tominaga M, Ichikawa M, et al. Relationship between regulatory and type 1 T cells in dogs with oral malignant melanoma. Microbiol Immunol 2002;54:152-159.
11. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006;6:295-307.
12. Matsushita N, Pilon-Thomas SA, Martin LM, et al. Comparative methodologies of regulatory T cell depletion in a murine melanoma model. J Immunol Methods 2008;333:167-179.
13. Langroudi L, Hassan ZM, Ebtekar M, et al. A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model. Int Immunopharmacol 2010;10:1055-1061.
14. Burton JH, Mitchell L, Thamm DH, et al. Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma. J Vet Intern Med 2011;25:920-926.
15. Gregory-Bryson E, Bartlett E, Kiupel M, et al. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11. BMC Cancer 2010;10:559.
16. Usher SG, Radford AD, Villiers EJ, et al. RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias. Exp Hematol 2009;37:65-77.
17. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216.
18. Veterinary Co-operative Oncology Group. Common Terminology Criteria for Adverse Events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.0. Vet Comp Oncol 2004;2:195-213.
19. Walter CU, Biller BJ, Lana SE, et al. Effects of chemotherapy on immune responses in dogs with cancer. J Vet Intern Med 2006;20:342-347.
20. Biller BJ, Elmslie RE, Burnett RC, et al. Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer. Vet Immunol Immunopathol 2007;116:69-78.
21. Faldyna M, Leva L, Knotigova P, et al. Lymphocyte subsets in peripheral blood of dogs-a flow cytometric study. Vet Immunol Immunopathol 2001;82:23-37.
22. Yancey MF, Merritt DA, White JA, et al. Distribution, metabolism, and excretion of toceranib phosphate (Palladia, SU11654), a novel tyrosine kinase inhibitor, in dogs. J Vet Pharmacol Ther 2010;33:154-161.
23. Motzer RJ, Hoosen S, Bello CL, et al. Sunitinib malate for the treatment of solid tumours: A review of current clinical data. Expert Opin Investig Drugs 2006;15:553-561.
24. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295:2516-2524.
25. Abrams VK, Hwang B, Lesnikova M, et al. A novel monoclonal antibody specific for canine CD25 (P4A10): Selection and evaluation of canine Tregs. Vet Immunol Immunopathol 2010;135:257-265.
26. Pinheiro D, Singh Y, Grant CR, et al. Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog. Immunology 2011;132:111-122.
27. Sharma S, Yang SC, Zhu L, et al. Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4 + CD25 + T regulatory cell activities in lung cancer. Cancer Res 2005;65:5211-5220.
28. Blansfield JA, Caragacianu D, Alexander HR 3rd, et al. Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clin Cancer Res 2008;14:270-280.
29. Zhang L, Smith KM, Chong AL, et al. In vivo antitumor and antimetastatic activity of sunitinib in preclinical neuroblastoma mouse model. Neoplasia 2009;11:426-435.
30. Ghiringhelli F, Menard C, Terme M, et al. CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 2005;202:1075-1085.
31. Schiavoni G, Sistigu A, Valentini M, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res 2011;71:768-778.
32. London CA. Tyrosine kinase inhibitors in veterinary medicine. Top Companion Anim Med 2009;24:106-112.
33. Lana S, U'Ren L, Plaza S, et al. Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs. J Vet Intern Med 2007;21:764-769.
34. Elmslie RE, Glawe P, Dow SW. Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. J Vet Intern Med 2008;22:1373-1379.