Lange Beverly J, Dinndorf Patricia, Smith Franklin O, Arndt Carola, Barnard Dorothy, Feig Stephen, Feusner James, Seibel Nita, Weiman Margie, Aplenc Richard, Gerbing Robert, Alonzo Todd A
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
J Clin Oncol. 2004 Jan 1;22(1):150-6. doi: 10.1200/JCO.2004.04.016.
Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show that in adults with acute myeloid leukemia (AML), IDA achieves higher remission rates and longer remission durations. In Children's Cancer Group Pilot Study CCG-2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in CCG-2891.
On days 1 through 3 and 10 through 14, patients received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients. Outcomes were compared with those of intensive timing in CCG-2891.
Treatment-related mortality after two courses of induction was not significantly different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9% with DNR/DNR. In course 1 of CCG-2941 IDA/IDA, 11% of patients withdrew compared with 1.5% in CCG-2891 (P <.001) and 5% in CCG-2941 IDA/DNR (P = not significant). Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v 36 days; P =.007), mean duration of course 1 by a week (P =.002), and risk of grade 3 or 4 hyperbilirubinemia (18% v 5%; P =.02). Toxicity of IDA/DNR was not different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P =.004). Remission induction, survival, and event-free survival rates were not significantly different from those of CCG-2891.
In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.
伊达比星（IDA）与柔红霉素（DNR）的随机对照研究表明，在成人急性髓系白血病（AML）患者中，IDA可实现更高的缓解率和更长的缓解持续时间。在儿童癌症组的CCG - 2941试点研究中，我们评估了在CCG - 2891中使用的基于柔红霉素的强化诱导治疗（DNR/DNR）中，用1 mg IDA替代4 mg DNR的毒性和可行性。
在第1至3天以及第10至14天，患者接受两个疗程的地塞米松、阿糖胞苷、6 - 硫鸟嘌呤、依托泊苷和IDA治疗（IDA/IDA）。在65例患者入组后，毒性反应促使对其余28例患者在第10至14天将IDA替换为DNR（IDA/DNR）。将结果与CCG - 2891中的强化治疗结果进行比较。
三个治疗方案在两个疗程诱导治疗后的治疗相关死亡率无显著差异：IDA/IDA方案为14%，IDA/DNR方案为7%，DNR/DNR方案为9%。在CCG - 2941的IDA/IDA方案的第1疗程中，11%的患者退出，而CCG - 2891中为1.5%（P <.001），CCG - 2941的IDA/DNR方案中为5%（P = 无显著差异）。与CCG - 2891的DNR/DRN方案相比，CCG - 2941的IDA/IDA方案使住院天数增加（43天对36天；P =.007），第1疗程的平均持续时间增加了一周（P =.002），3级或4级高胆红素血症的风险增加（18%对5%；P =.02）。IDA/DNR方案的毒性与CCG - 2891中DNR/DNR方案的毒性无差异。CCG - 2941中第7天骨髓原始细胞百分比的平均值为11.4%，而CCG - 2891中为21.1%（P =.004）。缓解诱导率、生存率和无事件生存率与CCG - 2891相比无显著差异。
在CCG - 2941中，IDA过度的毒性和患者退出情况超过了其早期反应的潜在益处。
