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Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma.
- Source :
-
Veterinary and comparative oncology [Vet Comp Oncol] 2011 Dec; Vol. 9 (4), pp. 275-82. Date of Electronic Publication: 2011 Mar 08. - Publication Year :
- 2011
-
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.<br /> (© 2011 Blackwell Publishing Ltd.)
- Subjects :
- Animals
California
Cat Diseases pathology
Cats
Drug Combinations
Female
Head and Neck Neoplasms drug therapy
Head and Neck Neoplasms pathology
Hospitals, Animal
Male
Mouth Neoplasms veterinary
Neoplasms, Squamous Cell drug therapy
Neoplasms, Squamous Cell pathology
Ornithine Decarboxylase administration & dosage
Ornithine Decarboxylase Inhibitors
Polyamines administration & dosage
Treatment Outcome
Cat Diseases drug therapy
Head and Neck Neoplasms veterinary
Neoplasms, Squamous Cell veterinary
Ornithine Decarboxylase therapeutic use
Polyamines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5829
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Veterinary and comparative oncology
- Publication Type :
- Academic Journal
- Accession number :
- 22077408
- Full Text :
- https://doi.org/10.1111/j.1476-5829.2011.00264.x