alexa A phase II study of alpha-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma.
Pharmaceutical Sciences

Pharmaceutical Sciences

Biochemistry & Pharmacology: Open Access

Author(s): Meyskens FL, Kingsley EM, Glattke T, Loescher L, Booth A

Abstract Share this page

Abstract Difluoromethylornithine (DFMO) is an irreversible enzyme-activated inhibitor of ornithine decarboxylase, a key enzyme in polyamine synthesis. We have screened for potential anti-cancer activity of DFMO using a clonogenic assay, which suggested that melanoma might have sensitivity to this agent. Accordingly, we have performed a phase II trial of DFMO (2 g/m2 po q 8 h) in 24 patients, 21 of whom were evaluable for response. One patient achieved a complete response of a large subcutaneous mass for 11 months. Although stabilization is frequently difficult to measure, seven patients appeared to stabilize previously active disease, with a median duration of response of eight weeks. Toxicity was significant and DFMO was discontinued in five patients due to side effects - hearing loss alone in four and hearing loss associated with thrombocytopenia in the fifth patient. Hearing changes occurred in ten patients. Other side effects were mild. These data indicate that DFMO as a single agent may be an effective therapy for melanoma. A phase II trial of DFMO in previously untreated patients using a different schedule to decrease hearing loss is warranted. Additionally, several in vitro and animal models suggest that DFMO plus interferon are synergistic, and this combination might be used for a clinical trial as well.
This article was published in Invest New Drugs and referenced in Biochemistry & Pharmacology: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords