Bolwell B J, Cassileth P A, Gale R P
Hematology-Oncology Section, University of Pennsylvania School of Medicine, Philadelphia.
Leukemia. 1988 May;2(5):253-60.
High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.
大剂量阿糖胞苷(HDARAC)疗法越来越多地用于治疗血液系统恶性肿瘤。最近的数据表明,每12小时给予2 - 3 g/M²共10 - 12剂的HDARAC在急性髓性白血病的缓解诱导中与标准剂量的阿糖胞苷具有相当或更高的疗效。HDARAC对常规剂量耐药的个体也能产生缓解。据报道,含HDARAC的方案比以前的缓解后治疗方法能带来显著更高的长期无病生存率,但这尚未在对照试验中得到证实。HDARAC在急性淋巴细胞白血病中也有活性。由于静脉注射HDARAC能在脑脊液中达到高浓度,它可用于治疗中枢神经系统白血病,并且可能为急性淋巴细胞白血病提供足够的中枢神经系统预防。据报道,HDARAC在晚期非霍奇金淋巴瘤和急性期慢性髓性白血病中也有活性;目前正在研究其在这些情况下的最佳应用。HDARAC也已与其他药物联合使用。需要进行随机试验来确定这些联合用药是否比单独使用HDARAC更有效。除了强效的骨髓抑制作用外,HDARAC的剂量限制性毒性是小脑损伤。这种情况在50岁以上的患者中发生频率增加。HDARAC在血液系统恶性肿瘤中具有活性,如果与其他药物联合使用可能会进一步改善治疗效果。