title: Future chelation monotherapy and combination therapy strategies in thalassemia and other conditions. comparison of deferiprone, deferoxamine, ICL670, GT56-252, L1NAll and starch deferoxamine polymers.
abstract: Deferiprone (L1), and appropriate combinations with deferoxamine (DFO), can be used effectively for the treatment of thalassemia and other transfusional iron loading conditions. A number of experimental iron chelators such as deferasirox or ICL670 or Exjade (4-(3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl)-benzoic acid), deferitrin (4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and starch DFO polymers, are under clinical evaluation. ICL670 is the most advanced in development and appears to be effective in reducing liver iron in some patients but is overall ineffective in causing negative iron balance. It is also suspected that it is not effective in cardiac iron removal. Combination therapies using L1, DFO and new iron chelating drugs may cause higher efficacy and lower toxicity by comparison to monotherapies. However, several limitations including the high cost of the new chelating drugs may not facilitate the availability of these new treatments to the vast majority of thalassemia patients, most of whom live in developing countries.
authors.affiliation: Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus. pri_gjk@cylink.com.cy
authors.forename: George J
authors.initials: GJ
authors.lastname: Kontoghiorghes
mesh_terms: D001565:Benzoates / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000627:therapeutic use; D015913:Chelation Therapy / Q000191:economics / Q000639:trends*; D002986:Clinical Trials as Topic; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005544:Forecasting; D006432:Hemochromatosis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D015394:Molecular Structure; D011728:Pyridones / Q000627:therapeutic use; D013213:Starch / Q000627:therapeutic use; D013789:Thalassemia / Q000188:drug therapy* / Q000628:therapy; D013844:Thiazoles / Q000627:therapeutic use; D065227:Transfusion Reaction; D014230:Triazoles / Q000627:therapeutic use
chemical_list: C507647:1-allyl-2-methyl-3-hydroxypyrid-4-one; C120073:4'-hydroxydesazadesferrithiocin; C512702:40SD02; D001565:Benzoates; D002264:Carboxylic Acids; D006895:Hydroxyethyl Starch Derivatives; D007502:Iron Chelating Agents; D011728:Pyridones; D013844:Thiazoles; D014230:Triazoles; C062213:hydroxyethylstarch-deferoxamine; D000077543:Deferiprone; D013213:Starch; D003676:Deferoxamine; D000077588:Deferasirox