Skip to main content
SpringerLink
Log in

Clinical Studies of Metronomic Chemotherapy in Dogs

  • Chapter
  • First Online:
Metronomic Chemotherapy

Abstract

In the last decade metronomic chemotherapy has received increased interest in veterinary oncology. Indeed, low-dose metronomic chemotherapy has been shown an important stabilizing effect on cancer growth, conferring both prolonged clinical benefits and positive effects on the quality of life of patients. A number of studies have been performed in dogs on the efficacy of metronomic dosing of various chemotherapeutic drugs. Metronomic chemotherapy is offered as the treatment of choice for all pets with malignant tumors where owners are reluctant to embark on an aggressive therapy protocol. It is indicated in patients with organ failure in which the toxicity of chemotherapy may be fatal as well as in patients with an aggressive nature that would require sedation for each parenteral administration. Metronomic therapy induces minimal impact on the animal; it is a low-cost alternative and it is easy to administer. Moreover, it has been recently recognized that dogs affected by natural cancer serve as unique animal model for human tumors. For this reason, the metronomic chemotherapy experience in dogs could lead to innovative and unexplored schedules for humans. It may be used as a more accurate model than rodents with induced cancers for the extrapolation of dose, efficacy and safety profiles to humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gonzalez-Billalabeitia E et al (2009) Long-term follow-up of an anthracycline-containing metronomic chemotherapy schedule in advanced breast cancer. Breast J 15:551–553

    PubMed  Google Scholar 

  2. Laquente B, Vinals F, Germa JR (2007) Metronomic chemotherapy: an antiangiogenic scheduling. Clin Transl Oncol 9:93–98

    CAS  PubMed  Google Scholar 

  3. Miller KD, Sweeney CJ, Sledge GW Jr (2001) Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol 19:1195–1206

    CAS  PubMed  Google Scholar 

  4. Pasquier E, Andre N, Braguer D (2007) Targeting microtubules to inhibit angiogenesis and disrupt tumour vasculature: implications for cancer treatment. Curr Cancer Drug Targets 7:566–581

    CAS  PubMed  Google Scholar 

  5. Blansfield JA, Caragacianu D, Alexander HA III et al (2008) Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clin Cancer Res 14(1):270–280

    CAS  PubMed  Google Scholar 

  6. Bocci G, Nicolaou KC, Kerbel RS (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62(23):6938–6943

    CAS  PubMed  Google Scholar 

  7. Pasquier E, Kavallaris M, André N (2010) Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol 7(8):455–465

    PubMed  Google Scholar 

  8. Bocci G, Francia G, Man S et al (2003) Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci U S A 100(22):12917–12922

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Damber JE, Vallbo C, Albertsson P et al (2006) The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin. Cancer Chemother Pharmacol 58:354–360

    CAS  PubMed  Google Scholar 

  10. Park ST, Jang JW, Kim GD et al (2010) Beneficial effect of metronomic chemotherapy on tumor suppression and survival in a rat model of hepatocellular carcinoma with liver cirrhosis. Cancer Chemother Pharmacol 65:1029–1037

    CAS  PubMed  Google Scholar 

  11. Kerbel RS, Kamen BA (2004) Antiangiogenic basis of low-dose metronomic chemotherapy. Nat Rev Cancer 4:423–436

    CAS  PubMed  Google Scholar 

  12. Mutsaers AJ (2007) Chemotherapy: new uses for old drugs. Vet Clin North Am Small Anim Pract 37:1079–1090

    PubMed  Google Scholar 

  13. Bocci G, Fioravanti A, Orlandi P et al (2012) Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1. Neoplasia 14(9):833–845

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Burton JH, Mitchell L, Thamm DH et al (2011) Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma. J Vet Intern Med 25(4):920–926

    CAS  PubMed  Google Scholar 

  15. Tanaka H, Matsushima H, Mizumoto N et al (2009) Classification of chemotherapeutic agents based on their differential in vitro effects on dendritic cells. Cancer Res 69:6978–6986

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Tanaka H, Matsushima H, Nishibu A et al (2009) Dual therapeutic efficacy of vinblastine as a unique chemotherapeutic agent capable of inducing dendritic cell maturation. Cancer Res 69:6987–6994

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Al-Dissi AN, Haines DM, Singh B et al (2010) Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 in canine simple mammary gland adenocarcinomas. Can Vet J 51(10):1109–1114

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Qiu C, Lin DD, Wang HH et al (2008) Quantification of VEGF-C expression in canine mammary tumours. Aust Vet J 86(7):279–282

    CAS  PubMed  Google Scholar 

  19. Qiu CW, Lin DG, Wang JQ et al (2008) Expression and significance of PTEN and VEGF in canine mammary gland tumours. Vet Res Commun 32(6):463–472

    CAS  PubMed  Google Scholar 

  20. Queiroga FL, Pires I, Parente M et al (2011) COX-2 over-expression correlates with VEGF and tumour angiogenesis in canine mammary cancer. Vet J 189(1):77–82

    CAS  PubMed  Google Scholar 

  21. Restucci B, Papparella S, Maiolino P et al (2002) Expression of vascular endothelial growth factor in canine mammary tumors. Vet Pathol 39(4):488–493

    CAS  PubMed  Google Scholar 

  22. Giantin M, Aresu L, Benali S et al (2012) Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases and vascular endothelial growth factor in canine mast cell tumours. J Comp Pathol. doi:10.1016/j.jcpa.2012.01.011

    PubMed  Google Scholar 

  23. Patruno R, Arpaia N, Gadaleta CD et al (2009) VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous model. J Cell Mol Med 13(3):555–561

    CAS  PubMed  Google Scholar 

  24. Rebuzzi L, Willmann M, Sonneck K et al (2007) Detection of vascular endothelial growth factor (VEGF) and VEGF receptors Flt-1 and KDR in canine mastocytoma cells. Vet Immunol Immunopathol 115(3–4):320–333

    CAS  PubMed  Google Scholar 

  25. Yonemaru K, Sakai H, Murakami M et al (2006) Expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors (flt-1, flk-1, and flg-1) in canine vascular tumors. Vet Pathol 43(6):971–980

    CAS  PubMed  Google Scholar 

  26. Dickinson PJ, Sturges BK, Higgins RJ et al (2008) Vascular endothelial growth factor mRNA expression and peritumoral edema in canine primary central nervous system tumors. Vet Pathol 45(2):131–139

    CAS  PubMed  Google Scholar 

  27. Platt SR, Scase TJ, Adams V et al (2006) Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival. J Vet Intern Med 20(3):663–668

    PubMed  Google Scholar 

  28. Rossmeisl JH, Duncan RB, Huckle WR et al (2007) Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms. Am J Vet Res 68(11):1239–1245

    CAS  PubMed  Google Scholar 

  29. Shiomitsu K, Johnson CL, Malarkey DE et al (2009) Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours. Vet Comp Oncol 7(2):106–114

    CAS  PubMed  Google Scholar 

  30. Wolfesberger B, Guija de Arespacohaga A, Willmann M et al (2007) Expression of vascular endothelial growth factor and its receptors in canine lymphoma. J Comp Pathol 137(1):30–40

    CAS  PubMed  Google Scholar 

  31. Wolfesberger B, Tonar Z, Fuchs-Baumgartinger A et al (2012) Angiogenic markers in canine lymphoma tissues do not predict survival times in chemotherapy treated dogs. Res Vet Sci 92(3):444–450

    CAS  PubMed  Google Scholar 

  32. Wolfesberger B, Tonar Z, Witter K et al (2008) Microvessel density in normal lymph nodes and lymphomas of dogs and their correlation with vascular endothelial growth factor expression. Res Vet Sci 85(1):56–61

    CAS  PubMed  Google Scholar 

  33. Taylor KH, Smith AN, Higginbotham M et al (2007) Expression of vascular endothelial growth factor in canine oral malignant melanoma. Vet Comp Oncol 5(4):208–218

    CAS  PubMed  Google Scholar 

  34. Matiasek LA, Platt SR, Adams V et al (2009) Ki-67 and vascular endothelial growth factor expression in intracranial meningiomas in dogs. J Vet Intern Med 23(1):146–151

    CAS  PubMed  Google Scholar 

  35. Al-Dissi AN, Haines DM, Singh B et al (2007) Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor associated with tumor cell proliferation in canine cutaneous squamous cell carcinomas and trichoepitheliomas. Vet Pathol 44(6):823–830

    CAS  PubMed  Google Scholar 

  36. Maiolino P, De Vico G, Restucci B (2000) Expression of vascular endothelial growth factor in basal cell tumours and in squamous cell carcinomas of canine skin. J Comp Pathol 123(2–3):141–145

    CAS  PubMed  Google Scholar 

  37. de Queiroz GF, Dagli ML, Fukumasu H et al (2010) Vascular endothelial growth factor expression and microvascular density in soft tissue sarcomas in dogs. J Vet Diagn Invest 22(1):105–108

    PubMed  Google Scholar 

  38. Marchetti V, Giorgi M, Fioravanti A et al (2012) First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study. Invest New Drugs 30(4):1725–1730

    PubMed  Google Scholar 

  39. Troy GC, Huckle WR, Rossmeisl JH et al (2006) Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases. J Vet Intern Med 20(1):144–150

    CAS  PubMed  Google Scholar 

  40. Wergin MC, Kaser-Hotz B (2004) Plasma vascular endothelial growth factor (VEGF) measured in seventy dogs with spontaneously occurring tumours. In Vivo 18(1):15–19

    CAS  PubMed  Google Scholar 

  41. Aresu L, Aricò A, Comazzi S et al (2014) VEGF and MMP-9: biomarkers for canine lymphoma. Vet Comp Oncol 12(1):29–36. doi:10.1111/j.1476-5829.2012.00328

    CAS  PubMed  Google Scholar 

  42. Gentilini F, Calzolari C, Turba ME et al (2005) Prognostic value of serum vascular endothelial growth factor (VEGF) and plasma activity of matrix metalloproteinase (MMP) 2 and 9 in lymphoma-affected dogs. Leuk Res 29(11):1263–1269

    CAS  PubMed  Google Scholar 

  43. Zizzo N, Patruno R, Zito FA et al (2010) Vascular endothelial growth factor concentrations from platelets correlate with tumor angiogenesis and grading in a spontaneous canine non-Hodgkin lymphoma model. Leuk Lymphoma 51(2):291–296

    CAS  PubMed  Google Scholar 

  44. Clifford CA, Hughes D, Beal MW et al (2001) Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma. J Vet Intern Med 15(2):131–135

    CAS  PubMed  Google Scholar 

  45. Kato Y, Asano K, Mogi T et al (2007) Clinical significance of circulating vascular endothelial growth factor in dogs with mammary gland tumors. J Vet Med Sci 69(1):77–80

    CAS  PubMed  Google Scholar 

  46. Thamm DH, O’Brien MG, Vail DM (2008) Serum vascular endothelial growth factor concentrations and postsurgical outcome in dogs with osteosarcoma. Vet Comp Oncol 6(2):126–132

    CAS  PubMed  Google Scholar 

  47. de Queiroz GF, Dagli ML, Meira SA et al (2013) Serum vascular endothelial growth factor in dogs with soft tissue sarcomas. Vet Comp Oncol 11(3):230–235

    PubMed  Google Scholar 

  48. Nelius T, Rinard K, Filleur S (2011) Oral/metronomic cyclophosphamide-based chemotherapy as option for patients with castration-refractory prostate cancer: review of the literature. Cancer Treat Rev 37(6):444–455

    CAS  PubMed  Google Scholar 

  49. Mutsaers AJ (2009) Metronomic chemotherapy. Top Companion Anim Med 24(3):137–143

    PubMed  Google Scholar 

  50. Lana S, U’Ren L, Plaza S et al (2007) Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs. J Vet Intern Med 21:764–769

    PubMed  Google Scholar 

  51. VCOG (2004) 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 2(4):194–213

    Google Scholar 

  52. Elmslie RE, Glawe P, Dow SW (2008) Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. J Vet Intern Med 22(6):1373–1379

    CAS  PubMed  Google Scholar 

  53. Tripp CD, Fidel J, Anderson CL et al (2011) Tolerability of administration of lomustine in dogs with cancer. J Vet Intern Med 25:278–284

    CAS  PubMed  Google Scholar 

  54. Leach TN, Childress MO, Greene SN et al (2012) Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer. Vet Comp Oncol 10(2):102–112

    CAS  PubMed  Google Scholar 

  55. Choisunirachon N, Jaroensong T, Yoshida K et al (2013) Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model. Vet Comp Oncol. doi:10.1111/vco.12059

    PubMed  Google Scholar 

  56. Mitchell L, Thamm DH, Biller BJ (2012) Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J Vet Intern Med 26:355–362

    CAS  PubMed  Google Scholar 

  57. London CA, Hannah AL, Zadovoskaya R et al (2003) Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 9:2755–2768

    CAS  PubMed  Google Scholar 

  58. London CA, Malpas PB, Wood-Follis SL et al (2009) 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 15:3856–3865

    CAS  PubMed  Google Scholar 

  59. Giorgi M, Saccomanni G, Del Carlo S, Manera C, Lavy E (2012) Pharmacokinetics of intravenous and intramuscular parecoxib in healthy Beagles. Vet J 193:246–250

    CAS  PubMed  Google Scholar 

  60. Kerbel RS (2012) Strategies for improving the clinical benefit of antiangiogenic drug based therapies for breast cancer. J Mammary Gland Biol Neoplasia 7(3–4):229–239

    Google Scholar 

  61. Herschman HR (2004) Noninvasive imaging of reporter gene expression in living subjects. Adv Cancer Res 92:29–80

    Google Scholar 

  62. Greenhough A, Smartt HJM, Moore AE et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30:377–386

    CAS  PubMed  Google Scholar 

  63. Gupta GP, Nguyen DX, Chiang AC et al (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446:765–770

    CAS  PubMed  Google Scholar 

  64. Harris SG, Padilla J, Koumas L et al (2002) Prostaglandins as modulators of immunity. Trends Immunol 23:144–150

    CAS  PubMed  Google Scholar 

  65. Tsuji M, Kawano S, Tsujii S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716

    PubMed  Google Scholar 

  66. Dore’ M, Lanthier I, Sirois J (2003) Cyclooxygenase-2 expression in canine mammary tumors. Vet Pathol 40:207–212

    Google Scholar 

  67. Heller DA, Clifford CA, Goldschmidt MH et al (2005) Cyclooxygenase-2 expression is associated with histologic tumor type in canine mammary carcinoma. Vet Pathol 42:776–780

    CAS  PubMed  Google Scholar 

  68. Queiroga FL, Alves A, Pires I et al (2007) Expression of Cox-1 and Cox-2 in canine mammary tumors. J Comp Pathol 136:177–185

    CAS  PubMed  Google Scholar 

  69. Queiroga FL, Perez-Alenza MD, Silvan G, Pena L, Lopes C, Illera JC (2005) Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance. Anticancer Res 25:4269–4275

    CAS  PubMed  Google Scholar 

  70. L’eplattenier HF, Lai CL, van den Ham R et al (2007) Regulation of COX-2 expression in canine prostate carcinoma: increased COX-2 expression is not related to inflammation. J Vet Intern Med 21:776–782

    PubMed  Google Scholar 

  71. Mohammed SI, Khan KNM, Sellers RS et al (2004) Expression of cyclooxygenase-1 and 2 in naturally-occurring canine cancer. Prostaglandins Leukot Essent Fatty Acids 70:479–483

    CAS  PubMed  Google Scholar 

  72. Sorenmo KU, Goldschmidt MH, Shofer FS et al (2004) Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of cyclooxygenase inhibitors in canine prostatic carcinoma. Vet Comp Oncol 2:13–23

    CAS  PubMed  Google Scholar 

  73. Tremblay C, Dore’ M, Boschler PN et al (1999) Induction of prostaglandin G/H synthase-2 in a canine model of spontaneous prostatic adenocarcinomas. J Natl Cancer Inst 91:1398–1403

    CAS  PubMed  Google Scholar 

  74. Khan KN, Knapp DW, Denicola DB et al (2000) Expression of cyclooxygeanse-2 in transitional cell carcinoma of the urinary bladder in dogs. Am J Vet Res 61:478–481

    CAS  PubMed  Google Scholar 

  75. Knottenbelt C, Mellor D, Nixon C et al (2006) Cohort study of COX-1 and COX-2 expression in canine rectal and bladder tumours. J Small Anim Pract 47:196–200

    CAS  PubMed  Google Scholar 

  76. Lee JY, Tanabe S, Shimohira H et al (2007) Expression of cyclooxygenase-2, P-glycoprotein and multi-drug resistance-associated protein in canine transitional cell carcinoma. Res Vet Sci 83:210–216

    CAS  PubMed  Google Scholar 

  77. Boria PA, Murry DJ, Bennett PF et al (2004) Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc 224:388–394

    CAS  PubMed  Google Scholar 

  78. Borzacchiello G, Paciello O, Papparella S (2004) Expression of cyclooxygenase-1 and −2 in canine nasal carcinomas. J Comp Pathol 131:70–76

    CAS  PubMed  Google Scholar 

  79. Borzacchiello G, Russo V, Russo M (2007) Immunohistochemical expression of cyclooxygenase-2 in canine ovarian carcinomas. J Vet Med Sci 54:247–249

    CAS  Google Scholar 

  80. Impellizeri JA, Esplin DG (2008) Expression of cyclooxygenase-2 in canine nasal carcinomas. Vet J 176:408–410

    CAS  PubMed  Google Scholar 

  81. Khan KNM, Stanfield KM, Trakovic D et al (2001) Expression of cyclooxygenase-2 in canine renal cell carcinoma. Vet Pathol 38:116–119

    CAS  PubMed  Google Scholar 

  82. Kleiter M, Malarkey DE, Ruslander DE et al (2004) Expression of cyclooxygenase-2 in canine epithelial nasal tumors. Vet Radiol Ultrasound 45:255–260

    PubMed  Google Scholar 

  83. Mullins MN, Lana SE, Dernell WS et al (2004) Cyclooxygenase-2 expression in canine appendicular osteosarcomas. J Vet Intern Med 18:859–865

    PubMed  Google Scholar 

  84. Rossmeisl JH Jr, Robertson JL, Zimmerman KL et al (2009) Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas. Vet Comp Oncol 7:173–180

    CAS  PubMed  Google Scholar 

  85. Brunelle M, Sartin EA, Wolfe LG et al (2006) Cyclooxygenase-2 expression in normal and neoplastic canine mammary cell lines. Vet Pathol 43:656–666

    CAS  PubMed  Google Scholar 

  86. Pronovost N, Suter MM, Mueller E et al (2004) Expression and regulation of cyclooxygenase-2 in normal and neoplastic canine keratinocytes. Vet Comp Oncol 2:222–233

    CAS  PubMed  Google Scholar 

  87. Wolfesberger B, Walter I, Hoelzl C et al (2006) Antineoplastic effect of the cyclooxygenase inhibitor meloxicamon canine osteosarcoma cells. Res Vet Sci 80:308–316

    CAS  PubMed  Google Scholar 

  88. Knapp DW, Richardson RC, Chan TCK et al (1994) Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 8:273–278

    CAS  PubMed  Google Scholar 

  89. Mohammed SI, Bennett PF, Craig BA et al (2002) Effects of the cyclooxygenase inhibitor, piroxicam, on tumor response, apoptosis and angiogenesis in a canine model of human invasive urinary bladder cancer. Cancer Res 62:356–358

    CAS  PubMed  Google Scholar 

  90. Mutsaers AJ, Mohanmed SI, DeNicola DB et al (2005) Pretreatment tumor prostaglandin E2 concentration and cyclooxygenase-2 expression are not associated with the response of canine naturally occurring invasive urinary bladder cancer to cyclooxygenase inhibitor therapy. Prostaglandins Leukot Essent Fatty Acids 72:181–186

    CAS  PubMed  Google Scholar 

  91. Schmidt BR, Glickman NW, De Nicola DB et al (2001) Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs. J Am Vet Med Assoc 218:1783–1786

    CAS  PubMed  Google Scholar 

  92. London CA, Hannah AL, Zadovoskaya R et al (2003) Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 9(7):2755–2768

    Google Scholar 

  93. Shchemelinin I, Sefc L, Necas E (2006) Protein kinases, their function and implication in cancer and other diseases. Folia Biologica (Praha) 52:81–100

    CAS  Google Scholar 

  94. Pryer NK, Lee LB, Zadovaskaya R et al (2003) Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors. Clin Cancer Res 9:5729–5734

    CAS  PubMed  Google Scholar 

  95. Frost D, Lasota J, Miettinen M (2003) Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet Pathol 40:42–54

    CAS  PubMed  Google Scholar 

  96. Wakeling AE (2005) Inhibitors of growth factor signalling. Endocr Relat Cancer 12(Suppl 1):183–187

    Google Scholar 

  97. Wanebo HJ, Argiris A, Bergsland E et al (2006) Targeting growth factors and angiogenesis; using small molecules in malignancy. Cancer Metastasis Rev 25:279–292

    PubMed  Google Scholar 

  98. Isotani M, Ishida N, Tominaga M et al (2008) Effect of tyrosine kinase inhibition by imatinib mesylate on mast cell tumors in dogs. J Vet Intern Med 22(4):985–988

    CAS  PubMed  Google Scholar 

  99. Marconato L, Bettini G, Giacoboni C et al (2008) Clinicopathological features and outcome for dogs with mast cell tumors and bone marrow involvement. J Vet Intern Med 22(4):1001–1007

    CAS  PubMed  Google Scholar 

  100. Hahn KA, Ogilvie G, Rusk T et al (2008) Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med 22:1301–1309

    CAS  PubMed  Google Scholar 

  101. Finke JH, Rini B, Ireland J et al (2008) Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 14:6674–6682

    CAS  PubMed  Google Scholar 

  102. Kenyon BM, Browne F, D’Amato RJ (1997) Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res 64(6):971–978

    CAS  PubMed  Google Scholar 

  103. Farese JP, Fox LE, Detrisac CJ et al (2004) Effect of thalidomide on growth and metastasis of canine osteosarcoma cells after xenotransplantation in athymic mice. Am J Vet Res 65(5):659–664

    CAS  PubMed  Google Scholar 

  104. Marconato L, Buchholz J, Keller M, Bettini G, Valenti P, Kaser-Hotz B (2013) Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: a pilot study. Vet Comp Oncol 11(2):101–112

    CAS  PubMed  Google Scholar 

  105. Paoloni MC, Khanna C (2007) Comparative oncology today. Vet Clin North Am Small Anim Pract 37(6):1023–1032

    PubMed Central  PubMed  Google Scholar 

  106. Bettini G, Morini M, Marconato L et al (2010) Association between environmental dust exposure and lung cancer in dogs. Vet J 186(3):364–369

    PubMed  Google Scholar 

  107. Bukowski JA, Wartenberg D, Goldschmidt M (1998) Environmental causes for sinonasal cancers in pet dogs, and their usefulness as sentinels of indoor cancer risk. J Toxicol Environ Health 54(7):579–591

    CAS  Google Scholar 

  108. Marconato L, Leo C, Girelli R et al (2009) Association between waste management and cancer in companion animals. J Vet Intern Med 23(3):564–569

    CAS  PubMed  Google Scholar 

  109. Lindblad-Toh K, Wade CM, Mikkelsen TS et al (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438(7069):803–819

    CAS  PubMed  Google Scholar 

  110. Ostrander EA, Giger U, Lindblad-Toh K (2006) The dog and its genome, Cold Spring Harbor Monograph Series. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  111. Gordon I, Paoloni M, Mazcko C et al (2009) The comparative oncology trials consortium: using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS Med 6(10):e1000161

    PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Clinics, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, Pisa, 56122, Italy

    Veronica Marchetti & Mario Giorgi

Authors
  1. Veronica Marchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Giorgi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Veronica Marchetti .

Editor information

Editors and Affiliations

  1. Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Guido Bocci

  2. Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA

    Giulio Francia

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Marchetti, V., Giorgi, M. (2014). Clinical Studies of Metronomic Chemotherapy in Dogs. In: Bocci, G., Francia, G. (eds) Metronomic Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43604-2_19

Download citation

Publish with us

Policies and ethics

Search

Navigation