Volger W R, Weiner R S, Moore J O, Omura G A, Bartolucci A A, Stagg M
Emory University, Atlanta, GA, USA.
Leukemia. 1995 Sep;9(9):1456-60.
A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.
一项III期临床试验旨在确定针对急性髓细胞白血病采用更强化的诱导和巩固治疗是否能提高缓解率并延长生存期。一个次要目标是确定使用非交叉耐药药物是否比诱导治疗中使用的相同药物更有效。年龄在15至50岁之间的未经治疗的白血病患者，在连续10天输注阿糖胞苷的前3天给予柔红霉素45mg/m²，阿糖胞苷初始剂量为2000mg/m²，但因毒性降至100mg/m²。年龄在36岁以下且达到完全缓解且有组织相容性供体的患者被分配到移植组。其余患者随机接受三个巩固治疗组之一：A组，阿糖胞苷200mg/m²，每日1次，共7天，柔红霉素45mg/m²，每日1次，共3天，共三个疗程；B组，先进行一个疗程的A组治疗，随后给予安吖啶120mg/m²，每日1次，共5天，然后连续5天输注阿扎胞苷，150mg/m²/天；C组，硫鸟嘌呤和阿糖胞苷，每12小时100mg/m²，柔红霉素10mg/m²，每日1次，共5天，共三个疗程，随后进行四个维持疗程，阿糖胞苷100mg/m²，每日1次，共5天，柔红霉素45mg/m²，每13周2天。从1981年到1986年，398例符合条件的患者入组，219例达到完全缓解。29例患者中有5例出现致命的胃肠道毒性后，阿糖胞苷的初始诱导剂量降低。只有11例患者被分配到移植组。巩固治疗组之间无显著差异。A、B、C三组的5年无病生存率分别为38%、31%和27%。采用诱导治疗中相同或不同药物进行强化巩固治疗与低剂量巩固治疗后进行维持治疗效果相同。
