Deferoxamine (DFO) in tumor therapy

Several studies an consistent with the hypothesis that avaible iron may have a role in promoting tumor cell growth with different biological nwcheninns. For this reason, many studies have been carried out to demoitrate the antitum activity of DFO. an iron chdator with a high affinity for ferritin-bound iron, DJPO u a potent inhibitor of DNA synthesis in human lymphocytes and all tumor cell linei and appear to arrest cells at or just before s phase of the mil proliferation cycle. Et it prawned that the toxicity is due to reversible inhibit ion of ribonucleotidft redutase that limiti DMA lynthesii. DFO it not myelontppmnve 'ik most dumolherateutic drugs. In particular, the effects of DFO have been studied in pis with neuroWiHoma, where ferritin it in part tumor derived and high concentration correlate with poor uot-oomc.Iti 1990 we initiated a phaM Q trial to determine the activity of a (ingle 5-day coune of DFO given as -hour IV infution daily tor 5 days at ISQ/mg/kg/day in 9 pti with neuroblaftonia Within 7 dayi of trulnwnt completion we obwrved recpoiu in 7/9 pu. and a decreaie in bone marrow infiltratiom and in 1/9 p, a reduction in tumor mats. From 1992 more than 100 pu. entered into a cooperative study where DFO wai followed by multiagenl chemotherapy (D-CECaT protocol) 57/100 pti. with Mage 3 and stage 4 neurobilattoma were évaluable for mpom and there were 24 CR, 5 VOPR, 21 PR, 3 MR and 4PD, It still remains to be demonstrated if improved induction in the treatment of pti with adviuwed netiroblaclOfna is cauwd by the addition of DFO or by the cytotoxic regimen atone. Further experimental and clinical studies with DFO are required to establish the exact role of DFO in the therapy of cancer.