title: Targeted combined aerosol chemotherapy in dogs and radiologic toxicity grading.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, 900 E. Campus Drive, Columbia, MO 65211, USA. seltingk@missouri.edu
authors.forename: Kim
authors.initials: K
authors.lastname: Selting
authors.forename: Stephanie
authors.initials: S
authors.lastname: Essman
authors.forename: Carol
authors.initials: C
authors.lastname: Reinero
authors.forename: Keith R
authors.initials: KR
authors.lastname: Branson
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Henry
authors.forename: Nellie
authors.initials: N
authors.lastname: Owen
authors.forename: Vamsi P
authors.initials: VP
authors.lastname: Guntur
authors.forename: J Clifford
authors.initials: JC
authors.lastname: Waldrep
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhand
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002404:Catheterization; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D009330:Nebulizers and Vaporizers; D011859:Radiography; D013997:Time Factors; D014018:Tissue Distribution; D000093542:Gemcitabine
chemical_list: D000336:Aerosols; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine