New chemotherapeutic agents in acute myeloid leukemia.
Only two classes of chemotherapeutic agents have shown activity in acute myeloid leukemia (AML): ara-C and topoisomerase II reactive agents. Frontline combinations of these agents produce complete response (CR) rates of 70% and long-term event free survival rates of 25%. New agents with different mechanisms of action are being explored. Nucleoside analogs such as chlorodeoxyadenosine (2-CdA) or fludarabine have shown single-agent efficacy and may be synergistic with ara-C. Combination therapy with ara-C and nucleoside analogs have shown promising results both as salvage therapy and in newly diagnosed patients. Combinations of topotecan with ara-C, VP16, and anthracyclines are being pursued, as is testing of other Topo-I inhibitors. Hypomethylating agents (5-azacytidine, decitabine) are showing activity in AML, producing CR rates of 5% to 30% as AML salvage therapy as a single agent, and 40%-60% in combinations. Decitabine may be synergistic with topo I inhibitors, biologic agents, and differentiating agents. Homoharringtonine has modest anti-AML activity, with CR rates of 10% to 30% as salvage therapy. Other classes of agents worthy of continuing investigation are platinum analogs and agents with novel mechanisms of action such as tallimustine.
Kantarjian
H M
HM
Department of Hematology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Estey
E H
EH
Keating
M A
MA
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D012176:Retinoids / Q000627:therapeutic use; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins; D016376:Oligonucleotides, Antisense; D012176:Retinoids; D003561:Cytarabine; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine