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Background Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently. Hypothesis/Objectives Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs. Animals Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated. Methods Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred. Results Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4‐10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3‐34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim. Conclusions and Clinical Importance All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD.

Background Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. Hypothesis/objectives We hypothesized that dogs with OSA could be treated safely by ex vivo activated T-cells that were generated by autologous cancer vaccination and supported by interleukin-2 (IL-2) treatment with survival more than twice that reported for amputation alone. Animals Osteosarcoma-bearing dogs (n = 14) were enrolled in a single-arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study. Methods Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T-cell-activating agent. Activated product was transfused and 5 SC IL-2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months. Results Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease-free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days. Conclusions and clinical importance This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival.

Background Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. Hypothesis/Objectives We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. Animals Fourteen client-owned dogs were prospectively enrolled. Methods Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. Results A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). Conclusions and Clinical Importance Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.