Losartan, toceranib, and carboplatin combination therapy for progressive pulmonary metastasis in canine osteosarcoma: a case report.

Osteosarcoma (OSA) is the most common and aggressive primary bone tumor in dogs. OSA frequently metastasizes to the lungs and has a poor prognosis despite current standard treatment. This case report described the clinical course of a 3-year-old castrated male Jindo dog diagnosed with right tibial OSA and a pre-existing pulmonary metastasis. Initially, the patient received adjuvant chemotherapy and maintained a stable disease state for approximately five months (21 weeks from initial diagnosis) until radiographic and computed tomography (CT) examinations revealed progressive pulmonary metastasis.In response to this progression, the treatment was shifted to a triple-combination regimen of carboplatin, high-dose losartan (angiotensin II type 1 receptor blocker [ARB], 10 mg/kg PO BID), and toceranib (2.75 mg/kg PO EOD). Nine weeks (30 weeks from diagnosis) after initiating this new regimen, a comprehensive CT re-evaluation demonstrated a significant positive response, marked by the radiographic disappearance of pulmonary nodules and complete resolution of the pleural effusion. This substantial improvement indicated a potential clinical benefit of the triple-combination regimen, which may suggest a synergistic effect when used alongside concurrent carboplatin cycles, in addition to losartan’s proposed capacity to remodel the tumor microenvironment (TME) and enhance toceranib efficacy. However, following the conclusion of the carboplatin cycles at week 30, the patient’s condition ultimately deteriorated despite the continuation of losartan and toceranib combination therapy, confirming extensive disease progression by week 40. A subsequent attempt with doxorubicin as a third-line agent resulted in severe adverse effects, including bone marrow suppression and life-threatening neutropenia, leading to the patient’s death shortly thereafter (43 weeks from diagnosis).This case presents a notable clinical observation of a favorable short-term response of high-dose losartan in combination with toceranib for progressive pulmonary metastatic OSA, potentially through favorable TME modulation. It also highlighted the inherent virulence of canine OSA and the challenges in achieving sustained long-term control. The development of innovative multimodal therapeutic approaches for the management of canine OSA is critically important.