The updated VCOG‐CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG‐CTCAE v1.0 and v1.1 were consulted for input, and additional co‐authors sought for expansion and refinement of the adverse event (AE) categories. VCOG‐CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural‐specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision‐making process applied to determination of dose‐limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

Medical records of 42 cats treated with mandibulectomy for oral neoplasia at eight institutions were reviewed to determine morbidity, progression-free interval, and survival time. Progression-free and survival rates at 1 and 2 years were 56% and 49%, and 60% and 57%, respectively. Cats with squamous cell carcinoma had significantly shorter survival than cats with fibrosarcoma or osteosarcoma. Seventy-two percent of cats were dysphagic or inappetent immediately postoperatively, and 12% never regained the ability to eat. Despite acute morbidity in 98% and long-term morbidity in 76% of cats, 83% of the 30 owners providing information were satisfied with the outcome of mandibulectomy.

Thymidine kinase (TK1) is a biomarker that correlates well with diagnosis and prognosis in certain canine cancers. Canine C-reactive protein (cCRP) is a widely accepted marker of inflammation correlated with increased risk and severity of various diseases. We evaluated serum TK1 and cCRP concentrations in apparently healthy dogs (n = 360). All dogs were followed up for a minimum of 6 months by health questionnaire. All dogs with cancer were identified using a proprietary dual-biomarker algorithm [termed Neoplasia Index (NI)]. Specificity of positive NI is 0.91 and high positive is 0.98. All-cause mortality was 20% in dogs with elevated cCRP and 3% in dogs with low cCRP. The performance of serum TK1 and cCRP as tools for screening for occult cancer is improved when evaluated together. Serum TK1 and cCRP (unified in the NI) are useful in the screening of occult canine cancer. cCRP is useful in screening for other serious diseases.

BackgroundSerum thymidine kinase type 1 (TK1) and canine C‐Reactive Protein (cCRP) might be useful in detecting dogs with cancer. Algorithms combining biomarkers are sometimes more accurate than results of individual tests.ObjectivesThe aim of this study was to compare serum TK1 and cCRP and Neoplasia Index (NI) in healthy and tumor‐bearing dogs.AnimalsClient‐owned dogs with (n = 253) and without (n = 156) cancer.MethodsRetrospective case–control study. Dogs with cancer were identified after submission of samples for commercial assay and case details were retrospectively collected. Healthy dogs (control) were identified through breed groups and health status was confirmed by health questionnaire for a minimum of 6 months. Serum TK1 activity was measured using a quantitative chemiluminescent assay and serum cCRP was measured using a quantitative ELISA assay.Results TK1 activity in the cancer (n = 253) and control group (n = 156) were 7.0 μ/L (median, range <0.5 to >100) and 1.8 μ/L (median, range 0.4 to 55.3), respectively (P < .001). cCRP concentrations in the cancer and control group were 6.0 mg/L (median, range <0.5 to >50) and 1.6 mg/L (median, range 0.09 to >50), respectively (P < .001). The NI in the cancer and control group were 6.4 (median, range 0–9.9) and 0.9 (median, range 0–7.6), respectively (P < .001). ROC AUCs of the NI and TK1 for all cancers were greater than 0.8, highest for lymphoma and histiocytic sarcoma.Conclusions and Clinical ImportanceIncreased concentrations of TK1 and cCRP, when present in dogs with cancer, might be useful in confirming a diagnosis and monitoring response to treatment.

BackgroundInterleukin (IL)-12 is a pro-inflammatory cytokine that mediates T-helper type 1 responses and cytotoxic T-cell activation, contributing to its utility as anti-cancer agent. Systemic administration of IL-12 often results in unacceptable toxicity; therefore, strategies to direct delivery of IL-12 to tumors are under investigation. The objective of this study was to assist the preclinical development of NHS-IL12, an immunocytokine consisting of an antibody, which targets necrotic tumor regions, linked to IL-12. Specifically this study sought to evaluate the safety, serum pharmacokinetics, anti-tumor activity, and immune modulation of NHS-IL12 in dogs with naturally occurring cancers.Methodology/Principal FindingsA rapid dose-escalation study of NHS-IL12 administered subcutaneously to dogs with melanoma was conducted through the Comparative Oncology Trials Consortium (COTC). Eleven dogs were enrolled in four dose-escalation cohorts; thereafter, an additional seven dogs were treated at the defined tolerable dose of 0.8 mg/m2. The expanded cohort at this fixed dose (ten dogs in total) was accrued for further pharmacokinetics and pharmacodynamics assessment. NHS-IL12 levels, serum cytokine concentrations, and peripheral blood mononuclear cell characterization (post-treatment) and draining lymph node immune profiling, and tumor biopsies (pre- and post-treatment) were collected. Adverse events included thrombocytopenia, liver enzymopathies, fever, and vasculitis. Correlation between interferon (IFN)-γ induction, adverse events, and NHS-IL12 exposure (maximum concentration and area under the concentration-time curve) were dose-dependent. Serum IL-10 levels and intratumoral CD8+ populations increased after treatment. Partial responses, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, were observed in two dogs treated with NHS-IL12 0.8 mg/m2 and 1.6 mg/m2.Conclusions/SignificanceNHS-IL12 was administered safely to dogs with melanoma and both immunologic and clinical activity was observed. This study successfully defined a narrow therapeutic window for systemic delivery of NHS-IL12 via the subcutaneous route. Results will inform the design and implementation of first-in-human clinical trials of NHS-IL12 in cancer patients.

The cumulative cardiotoxicity that occurs as a result of doxorubicin chemotherapy is irreversible and can affect both quality and quantity of life for the cancer patient. Cardiac troponin I (cTnI) is a sensitive and specific marker of cardiomyocyte death. The purpose of this retrospective study was to evaluate serum concentrations of cTnI in dogs with lymphoma or osteosarcoma given doxorubicin chemotherapy, and with known cardiac outcome, based on a minimum assessment by physical examination and thoracic radiography. Serum samples were also available for cTnI measurement from seven healthy dogs given intracoronary doxorubicin. Serial serum samples obtained before, during and after doxorubicin chemotherapy showed increased cTnI concentrations in some clinical patients following chemotherapy (P = 0.0083 compared to baseline), but this did not correlate with clinical signs of cardiomyopathy. In dogs that subsequently developed cardiomyopathy however, serum cTnI concentrations were elevated before clinical signs became evident (confirmed with echocardiography).

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Delivery of drugs by airway can minimize systemic toxicity and maximize local drug concentrations. Most cancers metastasize to the lungs. Our purpose was to determine platinum concentrations in the lung after targeted delivery of cisplatin (CDDP) with an intracorporeal nebulizing catheter (INC), and to determine the safety of escalating doses of inhaled CDDP. In anesthetized and mechanically ventilated healthy dogs, the INC (AeroProbe) was introduced via flexible bronchoscope into the right caudal lung lobe (RCLL) and CDDP (10 mg/m2) administered. Tissue and serum platinum concentrations were compared to those after an equivalent intravenous dose of CDDP (n = 3 dogs/group). In three additional dogs, pharmacokinetics were performed after inhaled and intravenous CDDP. Increasing dosages of inhaled CDDP (10, 15, 20, and 30 mg/m2) were then administered every 2 weeks. Dogs were sacrificed for postmortem examination at week 10. One additional dog was treated with a single dose of 30 mg/m2 and sacrificed 2 weeks later. Immediately following a single inhaled dose, mean CDDP levels were 44 times greater in the RCLL than in most other tissues and 15.6 times lower in the serum compared to intravenous dosing. Pharmacokinetic comparison showed that the AUC0-24h was similar (p = 0.72), but maximum serum concentration was fivefold lower after inhalation than intravenous delivery (p = 0.02). Escalating doses of inhaled CDDP (cumulative 75 mg/m2) produced no significant clinical or hematological effects, but there was radiographic and histologic evidence of severe pneumonitis with mild to moderate fibrosis confined to the RCLL. Radiographic and histologic changes were similar in the single, high-dose dog. Targeted inhaled CDDP achieved high concentrations in the treated lobe, with lower peak serum levels than after intravenous administration. Escalating doses of inhaled CDDP produced focal pneumonitis and fibrosis in the treated lung lobe with minimal clinical and hematologic effects. Targeted inhaled chemotherapy could be a promising method of treatment for primary and secondary lung tumors.