title: Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.
abstract: This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.
authors.affiliation: Mari Lowe Center for Comparative Oncology, Ryan Veterinary Hospital, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104-6010, USA. jrlewis@vet.upenn.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Lewis
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Brien
authors.affiliation: Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, School of Veterinary Medicine, CA 95616-8782, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Skorupski
authors.forename: Erika L
authors.initials: EL
authors.lastname: Krick
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Reiter
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jennings
authors.affiliation: Veterinary Surgical Associates, San Mateo, CA 94401, USA.
authors.forename: Carrie H
authors.initials: CH
authors.lastname: Jurney
authors.affiliation: School of Medicine, University of North Carolina, Chapel Hill 27599-7594, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Shofer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D002371:Cat Diseases / Q000188:drug therapy* / Q000473:pathology; D002415:Cats; D000518:Eflornithine / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006309:Hearing / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D011073:Polyamines / Q000032:analysis / Q000037:antagonists & inhibitors*; D011700:Putrescine / Q000032:analysis / Q000037:antagonists & inhibitors; D013095:Spermidine / Q000032:analysis / Q000037:antagonists & inhibitors; D013096:Spermine / Q000032:analysis / Q000037:antagonists & inhibitors; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D011073:Polyamines; D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine