NEW AGENTS FOR THE TREATMENT OF ACUTE MYELOGENOUS LEUKEMIA - FOCUS ONTOPOTECAN AND RETINOIDS

Topotecan and retinoids are among the most promising agents being eval uated for the treatment of acute myelogenous leukemia (AML), refractor y anemia with excess blasts (RAEB), and refractory anemia with excess blasts in transformation (RAEB-t). Single-agent topotecan is similar t o single-agent ara-C, but may be superior in patients with poor-progno sis chromosome abnormalities (ie, -5,-7). Topotecan plus ara-C is equi valent to topotecan alone in chronic myelomonocytic leukemia (CMML), b ut significantly more effective in RAEB and RAEB-t. Compared with sing le-agent ara-C, the complete remission (CR) rate with topotecan plus a ra-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 chemothera py using fludarabine, ara-C, and idarubicin, with or without ATRA and G-CSF, median survival among poor-prognosis patients was 6-7 months, b ut those who received ATRA did better than those who did not, primaril y 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.