Adjuvant anthracycline‐based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi‐institutional retrospective study of the Italian Society of Veterinary Oncology

Abstract

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% confidence interval [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 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .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 = .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. K E Y W O R D S dog, hemangiosarcoma, maximum tolerated chemotherapy, metastasis, metronomic chemotherapy, prognosis

Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study

“…Evaluating time to progression is an objective measurement of clinical efficacy that is free from bias introduced by dog owners’ decisions on euthanasia. However, given the aggressive nature of HSA in dogs, the lengths of progression-free interval and overall survival are typically similar among different study populations [ 10 , 15 , 50 , 51 ].…”

“…The autologous cancer vaccine also provides a significant survival advantage over surgery alone for dogs with stage III HSA, with minimal risk for adverse events. Many dog owners are concerned about adverse events associated with chemotherapy [ 20 ], and the anthracycline drugs have been associated with acute allergic reactions, GI upset, neutropenia, thrombocytopenia, and rarely cardiotoxicity [ 10 , 12 , 19 , 52 – 60 ]. In the present study, adverse events were common in the historical control group treated with standard anthracycline chemotherapy.…”

“…The spleen is the most common site of HSA in the dog, although liver, heart, and skeletal muscle may also be sites of origin [ 3 , 4 ]. After splenectomy, or wide surgical excision at other sites, reported median survival times range from 19 to 110 days, with death typically due to widespread metastasis which often results in significant hemorrhage [ 4 – 10 ]. Dogs with metastatic disease at the time of diagnosis (stage III) have a poor prognosis, with reported median survival times from 23 to 40 days following surgical removal of the primary tumor [ 5 , 9 , 10 ].…”

“…However, the addition of dacarbazine has been reported to increase the median survival time to > 550 days in a group of 9 dogs with stage II HSA [ 16 ]. Doxorubicin chemotherapy is modestly effective for dogs with stage III HSA, extending the median survival time to 107 to 140 days [ 10 , 17 ]. Altered expression of the ATP-binding cassette transporters ABCB1 and ABCG2 may be partly responsible for the inherent drug resistance observed in canine HSA [ 18 ].…”

“…In addition to the potential for prolonging survival in dogs with HSA, chemotherapy also has the potential to cause adverse events. In dogs with stage III HSA treated with anthracycline chemotherapy, 43.5% had adverse events, with 21.7% of treated dogs requiring hospitalization for supportive care [ 10 ]. The combination of doxorubicin, vincristine and cyclophosphamide (VAC protocol) to treat canine HSA caused neutropenia in 73% of dogs, 27% had severe gastrointestinal (GI) adverse events, and 13% developed sepsis [ 14 ].…”