Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas.
The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003606:Dacarbazine / Q000627:therapeutic use*; D000518:Eflornithine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000517:prevention & control / Q000556:secondary*; D005260:Female; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D008545:Melanoma / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013997:Time Factors
D004791:Enzyme Inhibitors; D003606:Dacarbazine; D000518:Eflornithine