title: Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma.
abstract: Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumour regression in mouse models of squamous cell carcinoma (SCC). The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase (ODC) inhibitor, DFMO, and to determine whether this therapy results in reduction in tumour polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumour biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose (MTD) of MQT 1426 when combined with DFMO was determined. Dose-limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, two cats experienced objective tumour regression and six cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted.
authors.affiliation: Department of Surgical and Radiological Sciences, University of California, Davis, CA 95616, USA. kskorups@ucdavis.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Skorupski
authors.forename: T G
authors.initials: TG
authors.lastname: O'Brien
authors.forename: T
authors.initials: T
authors.lastname: Guerrero
authors.forename: C O
authors.initials: CO
authors.lastname: Rodriguez
authors.forename: M R
authors.initials: MR
authors.lastname: Burns
mesh_terms: D000818:Animals; D002140:California; D002371:Cat Diseases / Q000188:drug therapy* / Q000473:pathology; D002415:Cats; D004338:Drug Combinations; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D006762:Hospitals, Animal; D008297:Male; D009062:Mouth Neoplasms / Q000662:veterinary; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D009955:Ornithine Decarboxylase / Q000008:administration & dosage / Q000627:therapeutic use*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009955:Ornithine Decarboxylase
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