Effect of a 1-hour IV infusion of doxorubicin on the development of cardiotoxicity in dogs as evaluated by electrocardiography and echocardiography.

Cardiotoxicity is a potentially life-threatening consequence of treatment with doxorubicin. Without reliable predictive or monitoring tests for early intervention, preventive methods are warranted. This study tested the hypothesis that a 1-hour infusion of doxorubicin would reduce the incidence of cardiotoxicity compared with historical incidences. Inclusion criteria for this retrospective trial were a minimum of three doses of doxorubicin administered as a 1-hour infusion in patients with at least two echocardiographic or electrocardiographic examinations during the course of treatment (median cumulative dose, 120 mg/m2). Of 133 dogs, 16 (12%) developed electrocardiographic abnormalities during or after treatment, which was statistically lower than the historical incidence of 17.7% (31 of 175 dogs). Only seven dogs (5.3%) developed abnormalities during the course of therapy. Three (2%) developed congestive heart failure.

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation.

The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies. Cancer Res; 77(11); 2869-80. ©2017 AACR.

Surgical and postoperative complications associated with tibial plateau leveling osteotomy in dogs with cranial cruciate ligament rupture: 397 cases (1998-2001).

OBJECTIVE: To identify surgical and postoperative complications of tibial plateau leveling osteotomy (TPLO) in dogs with rupture of the cranial cruciate ligament (CCL) and compare their incidence with those reported in the literature for other commonly performed CCL stabilization procedures. DESIGN: Retrospective study. ANIMALS: 346 dogs undergoing 397 TPLO procedures. PROCEDURE: Medical records of dogs undergoing 563 consecutive TPLO procedures were reviewed. Complications were recorded and assigned to groups on the basis of the period during which the complication was observed. RESULTS: 397 TPLOs met the criteria for inclusion in the study. Complications (n = 136) were recorded in 113 of the 397 (28%) procedures. Multiple complications developed in 10 dogs. In 19 dogs, a second surgery was performed to manage complications. Development of a complication after surgery was not associated with age or body weight of the dog, tibial plateau angle prior to stifle joint surgery, or experience of the surgeon. Factors significantly associated with complications were breed and performance of an arthrotomy concomitantly with TPLO. CONCLUSIONS AND CLINICAL RELEVANCE: TPLO was associated with development of numerous complications, some of which required surgical correction. Most complications resolved with nonsurgical treatment. Several complications were unique to the TPLO procedure because of the surgical technique and implants required. Although TPLO was associated with a greater number of complications than other CCL stabilization methods, the incidence of major complications was similar.