Targeted Combined Aerosol Chemotherapy in Dogs and Radiologic Toxicity Grading

Abstract

We investigated whether combination chemotherapy, targeted with the AeroProbe® Intracorporeal Nebulizing Catheter (INC), could be safely administered, and developed a radiologic grading scheme to monitor subclinical effects on the lungs. In anesthetized and mechanically ventilated healthy dogs (n = 3), we introduced the INC via a flexible bronchoscope into the right caudal lung lobe and administered escalating dosages of gemcitabine (1, 2, 3, or 6 mg/kg) followed by cisplatin (10 mg/m(2)). Treatments were performed every 2 weeks for 4 treatments and dogs were monitored weekly with physical examination, biochemical tests, and thoracic radiographs. Dogs were sacrificed 2 weeks after the final treatment and tissues examined histologically. A radiologic grading scheme was developed to monitor subclinical pulmonary toxicity. No significant side effects occurred in any dog. All dogs developed focal pneumonitis radiographically, and chronic, severe pneumonia with fibrosis histologically limited to the treated portion of the lung. Radiologic scores increased over time following increasing doses of chemotherapy. Targeted aerosol delivery of gemcitabine and cisplatin by INC was clinically well tolerated. This minimally invasive method is promising for lung cancer treatment, especially given the lack of clinical toxicity. The proposed radiologic grading scheme provides a method to monitor subclinical local drug toxicity.