Toceranib phosphate treatment for cancer-related high calcium in two

Abstract

CASE HISTORY: Two dogs, a 10-year-old male Siberian Husky cross and an 11-year-old male Cocker Spaniel were referred to a specialist veterinary hospital in Melbourne, Australia, for treatment of metastatic anal sac apocrine gland adenocarcinoma (ASAGAC) and concurrent hypercalcaemia (concentration of ionised calcium in serum > 1.5 mmol/L) of malignancy. CLINICAL FINDINGS: Case 1 had a left anal sac mass approximately 5.5 cm in diameter, enlarged sub-lumbar lymph nodes palpable on rectal examination and a concentration of ionised calcium in serum of 2.45 (reference range 1.2-1.32) mmol/L. Soft tissue opacities suspicious for metastatic pulmonary nodules were observed on thoracic radiographs. CT of Case 2 revealed bilateral anal gland masses (left: 4.7 × 3.2 cm; right: 2.8 × 2.1 cm) and a large, ill-defined, intrapelvic mass (7.0 × 6.0 cm) encompassing the medial iliac and internal iliac lymph nodes and intimately associated with the aortic blood vessels. Cytology of fine-needle aspirates of the anal gland masses of both dogs was consistent with ASAGAC. The owners of both dogs declined surgical intervention and medical management with toceranib phosphate was initiated in the gross disease setting. TREATMENT AND OUTCOME: Toceranib was initially administered at a dose of 2.5 mg/kg orally every other day in both dogs. Due to side effects from this medication, including hypocalcaemia, the dosing schedule was adjusted to Monday, Wednesday, and Friday with a dose range of 2.25-2.5 mg/kg. Both dogs remained alive, Case 1 after 519 days and Case 2 after 477 days, and were normocalcaemic at the time of writing. Both dogs experienced resolution of hypercalcaemia of malignancy while being treated with toceranib alone: hypercalcaemia was controlled for a total of 12 months in Case 1 and 15 months in Case 2. During treatment the anal sac mass of Case 1 remained approximately 5 cm in diameter and the sub-lumbar lymph node remained subjectively stable though no objective measurements were taken. Case 2's anal sac masses and intrapelvic lymph node mass subjectively reduced in size based on palpation. CLINICAL RELEVANCE: This case series highlights two instances where toceranib monotherapy effectively managed hypercalcaemia of malignancy secondary to metastatic ASAGAC. Despite the presence of extensive macroscopic neoplastic disease, both dogs achieved durable control of hypercalcaemia with toceranib treatment.ASAGAC: Anal sac apocrine gland adenocarcinoma; cRECIST: Canine response evaluation criteria in solid tumours; HHM: Humoral hypercalcaemia of malignancy; OST: Overall survival time; PFS: Progression-free survival; PTH: Parathyroid hormone; PTHrP: Parathyroid-related hormone peptide; RTK: Receptor tyrosine kinase; TKI: Tyrosine kinase inhibitor.