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

Invest New Drugs. 1986;4(3):257-62. doi: 10.1007/BF00179593.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Drug Evaluation
  • Eflornithine / administration & dosage
  • Eflornithine / adverse effects
  • Eflornithine / therapeutic use*
  • Female
  • Hearing / drug effects
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Ornithine Decarboxylase Inhibitors*
  • Tumor Stem Cell Assay


  • Antineoplastic Agents
  • Ornithine Decarboxylase Inhibitors
  • Eflornithine