Iron toxicity studies of quelamycin

A previous phase I study demonstrated excessive generalized toxicity (20 of 21 patients) and cardiotoxicity (eight of 21 patients) of single-day intermittent quelamycin (NSC-267703) treatment, and a modified schedule was recommended to overcome this acute toxicity. In the present study, 40 mg/m2 of quelamycin was administered iv on 2 or 3 consecutive days. This 2- or 3-day course was associated with a decrease in the incidence of general symptoms (five of nine patients) and a decrease in cardiotoxicity (none of nine patients). In addition, patients receiving multiple courses of quelamycin were evaluated. Clinical and pathologic findings supported the diagnosis of early hemochromatosis. In conclusion, quelaymcin administration was associated with acute and chronic iron-overloading toxicity. Acute iron toxicity was prevented by the administration of quelamycin at a dose of 40 mg/m2 iv on 3 consecutive days. On the other hand, hemochromatosis was an unexpected finding which requires further investigations before this drug is acceptable for broader studies.