A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma

Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL‐DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148–184]. The ½ year and one‐year survival was 41.2% (95% CI 24.8–56.9) and 22.7% (95% CI 9.9–37.4), respectively. In dogs treated with PL‐DOX, a desquamating dermatitis like palmar‐plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups.     

Metastatic synovial cell sarcoma in two cats

Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS has not previously been reported. In both cases, treatment consisted of limb amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary metastases were diagnosed in one cat 316 days postoperatively. This cat died of chronic renal failure 444 days after limb amputation. The second cat died of an acute pulmonary thromboembolism 41 days postoperatively without evidence of local tumour recurrence or metastatic disease.     

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi‐agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty‐six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1‐527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1‐202 days) and MST 40 days (range 1‐527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2‐87 days) and MST 24 days (range 3‐91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities.     

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.     

Treatment of vascular and soft-tissue sarcomas in dogs using an alternating protocol of ifosfamide and doxorubicin

A retrospective analysis was done to assess the toxicity and efficacy associated with an alternating chemotherapy protocol of ifosfamide (375 mg m^?2) and doxorubicin (30 mg m^?2) for adjuvant treatment of 39 dogs with sarcomas. Twelve dogs had various soft‐tissue sarcomas and 27 dogs had hemangiosarcoma (HSA). Complete blood counts were evaluated 7 days after the first dose of ifosfamide and doxorubicin. One dog had grade 4 neutropenia (<500 µL^?1) after treatment with ifosfamide and one dog had grade 3 neutropenia (500–1000 µL^?1) after treatment with doxorubicin. One dog treated with doxorubicin was hospitalized for 24 h due to vomiting. The median survival time (ST) for the 27 dogs with HSA treated by surgery and with doxorubicin/ifosfamide was 149 days (mean 366 days). Although the protocol of alternating ifosfamide and doxorubicin was well tolerated, it failed to result in a statistically significant improvement in the ST when compared to a historical population of dogs with stage 2 splenic HSA treated by surgery alone.     

Safety of concurrent administration of dexrazoxane and doxorubicin in the canine cancer patient

Doxorubicin may cause a rare but serious cardiotoxicity. Dexrazoxane is a cardioprotectant drug used to reduce the risk of cardiotoxicity in human patients. In this study, 25 tumour-bearing dogs were treated with concurrent doxorubicin and dexrazoxane. The total number of doses of dexrazoxane given was 54 (range 1-5 doses per dog, median 2 doses). Five dogs received more than 165 mg m(2) cumulative doxorubicin dose before starting dexrazoxane. Haematologic, gastrointestinal and cardiovascular toxicities were considered tolerable. The combination of doxorubicin with dexrazoxane was well tolerated with minimal side-effects in this patient cohort. Future studies are required to evaluate potential cardioprotective effects of dexrazoxane given concurrently with doxorubicin.     

The effects of baicalein on canine osteosarcoma cell proliferation and death

Flavonoids are a group of modified triphenolic compounds from plants with medicinal properties. Baicalein, a specific flavone primarily isolated from plant roots (Scutellaria baicalensis), is commonly used in Eastern medicine for its anti‐inflammatory and antineoplastic properties. Previous research shows greater efficacy for baicalein than most flavonoids; however, there has been little work examining their effects on sarcoma cells, let alone canine cells. Three canine osteosarcoma cell lines (HMPOS, D17 and OS 2.4) were treated with baicalein to examine cell viability, cell cycle kinetics, anchorage‐independent growth and apoptosis. Results showed that osteosarcoma cells were sensitive to baicalein at concentrations from approximately 1 to 25 μM. Modest cell cycle changes were observed in one cell line. Baicalein was effective in inducing apoptosis and did not prevent doxorubicin cell proliferation inhibition in all the cell lines. The mechanism for induction of apoptosis has not been fully elucidated; however, changes in mitochondrial permeability supersede the apoptotic response.