Inter-individual variations in drug responses are major concerns in cancer treatment in human and veterinary oncology. Consequently, preclinical models have been proposed to predict drug responses and determine optimal individualized therapy. We aimed to evaluate the clinical utility of in vitro drug sensitivity testing using a patient-derived cell culture model to select appropriate adjuvant therapies for dogs with solid tumors. We screened medical records of 126 dogs with suspected tumors, including 33 dogs with solid tumors (guided group, 16; empirical group, 17). Anticancer drugs used for adjuvant therapy were determined based on in vitro drug sensitivity testing (guided group) or histopathological examination (empirical group) results. Time to tumor progression (TTP) was compared between groups. The guided group had significantly longer TTP than the empirical group (949 vs. 109 days). Median TTPs were significantly longer in the guided group than in the empirical group for dogs with incomplete surgical margin (949 vs. 109 days), dogs with mitotic count < 20 per 10 high power fields (949 vs. 105 days), dogs with no evidence of metastatic disease at initial diagnosis (455 vs. 196 days), and dogs receiving tyrosine kinase inhibitors (949 vs. 109 days). Our study suggests that in vitro drug sensitivity testing may be a useful tool for optimizing adjuvant therapy in dogs with solid tumors.

A 13-year-old spayed female cocker spaniel was presented with a 2-month history of swelling in several digits and intermittent hindlimb lameness. Radiographs revealed marked soft-tissue swelling and periosteal new bone formation without cortical bone destruction, characteristic of hypertrophic osteopathy (HO), in the distal parts of all extremities except for the right forelimb. However, no notable findings were detected in thoracic radiographs. An ultrasonography indicated cranial bladder wall thickening, which resolved following antibiotic therapy. Computed tomographic angiography identified a potential underlying cause as an aberrant right subclavian artery (ARSA) originating from the aortic arch, compressing the esophagus and causing mild esophageal cranial dilation to the aberrant vessel. No other intrathoracic or neoplastic lesions were observed. Gastrointestinal symptoms, such as regurgitation, were absent. Although an ARSA was likely the cause of HO, surgical correction was declined by the owner. To the best of our knowledge, this is the first reported case of HO concurrent with ARSA in dogs.

The existence of considerable interpatient variability in pharmacokinetic exposure necessitates dose adjustment to avoid potential adverse events and suboptimal efficacy in targeted therapy. Exposure–response relationships for toceranib phosphate (TOC), the most commonly used tyrosine kinase inhibitor in veterinary oncology, remain unclear. Correlations between TOC exposure and efficacy and safety were evaluated in dogs with solid tumors in our study. Plasma TOC was analyzed at 6 and 48 h post-administration. For the 10 dogs in the exposure–response analysis, the mean interpatient variabilities in dose-normalized peak (C_max) and trough (C_min) concentrations were 29% and 61%, respectively. Dose-normalized C_max did not differ among weeks 1, 4, and 12 (p = 0.414), suggesting that steady-state plasma levels can be achieved within 1 week. Pharmacokinetic exposure at steady state was not significantly associated with efficacy (week 1 C_max, p = 0.941; average C_max, p = 0.548). C_max was positively but nonsignificantly associated with the risk of adverse events (week 1 C_max, p = 0.190; average C_max, p = 0.109). These findings suggest the value of pharmacokinetic monitoring in optimizing TOC dosage and reducing its adverse effects in dogs with solid tumors. Clinicians should consider plasma TOC when managing TOC treatment in small-animal practice.