[Principles of high-dose cytarabinoside treatment].
Ara-C can be regarded as an analogue of cytidine and of deoxycytidine. It is activated by a kinase system leading to Ara-CTP and inactivated by deaminases mainly to Ara-U. Resistance to Ara-C can develop by at least four mechanisms: decreased activation, increased inactivation, decreased half-life of intracellular Ara-CTP and decreased cellular incorporation. Following short-therm high-dose infusions, therapeutically significant concentrations in blood and cerebrospinal fluid can be achieved for 6-12 hrs. The concept of high dose Ara-C is thus based on solid biochemical and pharmacological data; its application in refractory leukemias and lymphomas and in leukemic meningeosis is, however, restricted by significant toxicity and by the reduced normal stem cell potential in these patients.
D000208:Acute Disease; D001853:Bone Marrow / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003561:Cytarabine / Q000097:blood / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000188:drug therapy*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D003561:Cytarabine
Grundlagen der hochdosierten Cytarabinosid-Behandlung.