Adjuvant anthracycline-based versus metronomic chemotherapy versus no medical treatment for dogs with metastatic splenic hemangiosarcoma: a multi-institutional retrospective study of the Italian Society of Veterinary Oncology.

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC, and 42 were not medically treated. Overall median TTP and ST were 50 (95% CI, 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 versus 52 days, P=0.025; median ST, 140 versus 58 days, P=0.023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P=0.017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma. This article is protected by copyright. All rights reserved.

[1]  C. London,et al.  The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma , 2018, The Journal of small animal practice.

[2]  L. Marconato,et al.  The use of low‐dose metronomic chemotherapy in dogs—insight into a modern cancer field , 2018, Veterinary and comparative oncology.

[3]  J. Munday,et al.  Does thalidomide prolong survival in dogs with splenic haemangiosarcoma? , 2018, The Journal of small animal practice.

[4]  A. Mutsaers,et al.  Adjuvant Doxorubicin with or without Metronomic Cyclophosphamide for Canine Splenic Hemangiosarcoma. , 2017, Journal of the American Animal Hospital Association.

[5]  L. Marconato,et al.  A retrospective analysis of chemotherapy switch suggests improved outcome in surgically removed, biologically aggressive canine haemangiosarcoma† , 2017, Veterinary and comparative oncology.

[6]  L. Marconato,et al.  Comparison of doxorubicin–cyclophosphamide with doxorubicin–dacarbazine for the adjuvant treatment of canine hemangiosarcoma , 2017, Veterinary and comparative oncology.

[7]  D. Thamm,et al.  Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document. , 2015, Veterinary and comparative oncology.

[8]  L. Price,et al.  Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001-2012). , 2015, Journal of the American Veterinary Medical Association.

[9]  W. Kisseberth,et al.  VAC protocol for treatment of dogs with stage III hemangiosarcoma. , 2013, Journal of the American Animal Hospital Association.

[10]  D. Knapp,et al.  Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma. , 2013, Journal of the American Veterinary Medical Association.

[11]  D. Knapp,et al.  Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer. , 2012, Veterinary and comparative oncology.

[12]  J. Bryan,et al.  Tolerability of metronomic administration of lomustine in dogs with cancer. , 2011, Journal of veterinary internal medicine.

[13]  S. Dow,et al.  Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. , 2008, Journal of veterinary internal medicine.

[14]  Tara N. Hammond,et al.  Prevalence of hemangiosarcoma in anemic dogs with a splenic mass and hemoperitoneum requiring a transfusion: 71 cases (2003-2005). , 2008, Journal of the American Veterinary Medical Association.

[15]  G. Monteith,et al.  Epirubicin in the adjuvant treatment of splenic hemangiosarcoma in dogs: 59 cases (1997-2004). , 2007, Journal of the American Veterinary Medical Association.

[16]  R. Poppenga,et al.  Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma. , 2007, Journal of veterinary internal medicine.

[17]  S. Dow,et al.  Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs. , 2007, Journal of veterinary internal medicine.

[18]  J. Modiano,et al.  Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation. , 2006, Experimental hematology.

[19]  P. Schultheiss A Retrospective Study of Visceral and Nonvisceral Hemangiosarcoma and Hemangiomas in Domestic Animals , 2004, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[20]  Robert S. Kerbel,et al.  The anti-angiogenic basis of metronomic chemotherapy , 2004, Nature Reviews Cancer.

[21]  F. Shofer,et al.  Efficacy and toxicity of a dose-intensified doxorubicin protocol in canine hemangiosarcoma. , 2004, Journal of veterinary internal medicine.

[22]  E. Hardie,et al.  Acute nontraumatic hemoabdomen in the dog: a retrospective analysis of 39 cases (1987-2001). , 2003, Journal of the American Animal Hospital Association.

[23]  R. Kerbel,et al.  Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. , 2003, Cancer research.

[24]  M. Piccart-Gebhart Mathematics and oncology: a match for life? , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  C. Couto,et al.  Efficacy and toxicity of VAC chemotherapy (vincristine, doxorubicin, and cyclophosphamide) in dogs with hemangiosarcoma. , 1991, Journal of veterinary internal medicine.

[26]  D. W. Hayden,et al.  Intracranial lesions in dogs with hemangiosarcoma. , 1989, Journal of veterinary internal medicine.

[27]  B. Powers,et al.  Splenomegaly in Dogs , 1989 .

[28]  M. Quinn,et al.  Low dose cyclophosphamide: Mechanisms of T cell modulation. , 2016, Cancer treatment reviews.

[29]  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. , 2004, Veterinary and comparative oncology.

[30]  E. Macewen,et al.  Canine hemangiosarcoma: retrospective analysis of 104 cases. , 1985, Journal of the American Veterinary Medical Association.