Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma

Katherine A Skorupski, T. G. O'Brien, T. Guerrero, C. O. Rodriguez, M. R. Burns

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalVeterinary and Comparative Oncology
Volume9
Issue number4
DOIs
StatePublished - Dec 2011

Fingerprint

Eflornithine
Phase II Clinical Trials
Clinical Trials, Phase I
ornithine
Felidae
squamous cell carcinoma
Polyamines
polyamines
Squamous Cell Carcinoma
clinical trials
mouth
cats
Cats
Maximum Tolerated Dose
remission
Neoplasms
therapeutics
neoplasms
dosage
toxicity

Keywords

  • Animal model
  • Cell signalling
  • Comparative oncology
  • Small animal
  • Tumour biology

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma. / Skorupski, Katherine A; O'Brien, T. G.; Guerrero, T.; Rodriguez, C. O.; Burns, M. R.

In: Veterinary and Comparative Oncology, Vol. 9, No. 4, 12.2011, p. 275-282.

Research output: Contribution to journalArticle

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