Amsacrine (m-AMSA): a new antineoplastic agent. Pharmacology, clinical activity and toxicity.
The synthetic aminoacridine derivative amsacrine (m-AMSA) is capable of preventing DNA from serving as a template in replication and DNA synthesis. This mechanism of action is similar to that of anthracyclines, but clinical evidence suggests the lack of cross-resistance. The recommended dosage in patients with solid tumors is 90-120 mg/m2 intravenously every 3-4 weeks. Despite the initial encouraging reports from experimental models, m-AMSA has shown no real impact in the treatment of patients with a wide variety of solid tumors. In relapsed acute nonlymphocytic leukemia, 20-30% of patients will achieve complete remission. An increased remission rate is obtained when m-AMSA is combined with other agents, especially with high-dose cytosine arabinoside, with a complete remission rate of 50-60% in relapsed patients. Currently, several phase III trials are evaluating m-AMSA combinations against daunorubicin-containing regimens in patients with previously untreated acute leukemia. The potential role of these regimens in this disease remains to be defined.
Hornedo
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Van Echo
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D000208:Acute Disease; D000609:Aminoacridines / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002330:Carmustine / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004261:DNA Replication / Q000187:drug effects; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D006321:Heart / Q000187:drug effects; D006689:Hodgkin Disease / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D007938:Leukemia / Q000188:drug therapy; D007939:Leukemia L1210 / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D012313:RNA / Q000096:biosynthesis; D013280:Stomatitis / Q000139:chemically induced
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine; D012313:RNA; D002330:Carmustine