Maintenance therapy with toceranib following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma

Abstract

BackgroundSpenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone.ResultsDogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days.ConclusionsThe use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma

“…Our findings were also similar to Gardner et al . () in which no improvement in disease‐free interval or survival time was noted with the addition of a maintenance protocol after completion of doxorubicin with toceranib. One of the targets of toceranib is VEGF which is also a target of MC (Albertsson et al .…”

A retrospective analysis of chemotherapy switch suggests improved outcome in surgically removed, biologically aggressive canine haemangiosarcoma

“…Switch maintenance has been recently investigated in canine stage I–II splenic HSA by administering the tyrosine kinase inhibitor toceranib phosphate. Toceranib mainly targets the stem cell factor receptor KIT, platelet derived growth factor receptor and vascular endothelial growth factor receptor (VEGFR), which are typically expressed by canine HSA …”

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR

“…Canine hemangiosarcoma and human angiosarcoma are both vasoformative sarcomas with similar microscopic appearance [13] that have often metastasized by the time they are diagnosed. Humans with angiosarcoma have an expected median survival of approximately 16 months [14]; dogs with HSA have a comparable, short median survival of 4 to 6 months when treated with the standard-of-care of surgery and adjuvant chemotherapy [15, 16]. Morbidity and mortality are usually caused by metastatic spread and/or acute internal hemorrhage secondary to tumor rupture.…”