New agents for the treatment of acute myelogenous leukemia: focus on topotecan and retinoids.
Topotecan and retinoids are among the most promising agents being evaluated for the treatment of acute myelogenous leukemia (AML), refractory anemia with excess blasts (RAEB), and refractory anemia with excess blasts in transformation (RAEB-t). Single-agent topotecan is similar to single-agent ara-C, but may be superior in patients with poor-prognosis chromosome abnormalities (ie, -5,-7). Topotecan plus ara-C is equivalent to topotecan alone in chronic myelomonocytic leukemia (CMML), but significantly more effective in RAEB and RAEB-t. Compared with single-agent ara-C, the complete remission (CR) rate with topotecan plus ara-C is comparable, although it offers special advantages in patients with the -5,-7 karyotype. In patients with poor-prognosis cytogenetics, the combination of cyclophosphamide, ara-C, and topotecan, plus all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) appears favorable. In a recent study of triple-agent chemotherapy using fludarabine, ara-C, and idarubicin, with or without ATRA and G-CSF, median survival among poor-prognosis patients was 6-7 months, but those who received ATRA did better than those who did not, primarily because it improved survival in those who did not achieve CR. G-CSF produced higher CR rates but had no effect on survival or disease-free survival.
Estey
E H
EH
University of Texas MD Anderson Cancer Center, Houston 77030, USA.
D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D012176:Retinoids / Q000627:therapeutic use; D019772:Topotecan / Q000627:therapeutic use
D000970:Antineoplastic Agents; D012176:Retinoids; D019772:Topotecan