High-dose chemotherapy in adult acute myeloid leukemia: rationale and results.
Preclinical studies and retrospective evaluations of clinical trials of a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid leukemia (AML). To maximize cure and remission rates at an acceptable cost in toxicity, many schedules and combinations of dose-intensive chemotherapy have been tested in recent years in patients with de novo disease, cytosine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and non-controlled studies. Our analysis indicates that high-dose Ara-C (HIDAC) used during induction results is no substantial benefit relative to conventional doses of drug. On the other hand, consolidation with HIDAC is a major advance in the treatment of this disease. In fact, in individuals less than 60 years of age and a favorable or intermediate-risk karyotype, HIDAC-based regimens have resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Yet, the role of HIDAC is irrelevant in younger individuals with an unfavorable cytogenetic pattern and detrimental in patients greater than 60 years of age. Since recently new cytotoxic agents have expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy still need to be performed to optimize schedules and combinations of drugs in patients with AML.
Stasi
R
R
Chair of Hematology, University of Rome Tor Vergata, S. Eugenio Hospital, Italy. mc2558@mclink.it
Venditti
A
A
Del Poeta
G
G
Aronica
G
G
Abruzzese
E
E
Pisani
F
F
Cecconi
M
M
Masi
M
M
Amadori
S
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D000970:Antineoplastic Agents; D003561:Cytarabine