Berman E, Arlin Z A, Gaynor J, Miller W, Gee T, Kempin S J, Mertelsmann R, Andreeff M, Reich L, Nahmias N
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York.
Leukemia. 1989 Feb;3(2):115-21.
Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.
96例初发急性非淋巴细胞白血病（ANLL）患者被随机分为两组，一组在第1 - 3天接受柔红霉素（50 mg/m²，静脉注射）；阿糖胞苷（Ara - C）（25 mg/m²，静脉推注），随后以160 mg/m²持续静脉输注，每日1次，共5天，以及6 - 硫鸟嘌呤（6 - TG）（100 mg/m²，口服），每12小时1次，每日1次，共5天（DAT方案）；另一组在第1 - 3天接受安吖啶（190 mg/m²，静脉注射），同时给予上述剂量的Ara - C和6 - TG（AAT方案）。达到完全缓解（CR）的患者随后接受两个疗程的巩固治疗，采用诱导缓解时相同的联合方案，但总剂量略有减少。年龄小于或等于40岁且有 HLA 匹配同胞供者的患者通常在巩固治疗后接受异基因移植。其余患者随后被随机分为接受维持治疗（长春新碱/甲氨蝶呤、环磷酰胺/6 - TG、柔红霉素/羟基脲和Ara - C/6 - TG交替周期）或不再接受进一步治疗。92例患者可评估疗效。接受DAT方案的46例患者中有25例（54%）达到CR，接受AAT方案的46例患者中有32例（70%）达到CR（p = 0.13）。然而，按年龄分层时，AAT方案在诱导缓解方面的优势具有统计学意义（p = 0.03）。此外，接受一个疗程AAT方案后达到CR的患者比接受一个疗程DAT方案的患者更多（48%对28%，p = 0.03）。AAT组的总生存期也有所改善（p = 0.01）。该方案维持治疗组随机入组的患者太少，无法进行有意义的解读。两组的非血液学毒性总体相当。总之，与接受DAT方案的患者相比，接受AAT方案的初发ANLL患者缓解率更高，生存期略长。有必要对这种药物联合方案在未经治疗的ANLL患者中进行进一步研究。
