Creutzig U, Körholz D, Niemeyer C M, Kabisch H, Graf N, Reiter A, Scheel-Walter H, Bender-Götze C, Behnisch W, Hermann J, Mann G, Ritter J, Zimmermann M
Universitäts-Kinderkliniken in Deutschland, Münster.
Klin Padiatr. 2000 Jul-Aug;212(4):163-8. doi: 10.1055/s-2000-9671.
Idarubicin (IDR) is one of the most effective, but also toxic drugs in the treatment of AML. The standard dose used in children and adults is 8-12 mg/m2 during induction.
To improve outcome, we increased the IDR dose from 12 mg/m2 (standard dose in study AML-BFM 93), applied over three days during induction therapy (AIE = Ara-C, Idarubicin, Etoposide) to 14 mg/m2 in a pilot study including 17 patients (16 with de novo AML, one with secondary AML). Outcome and toxicities were compared with the other patients of study AML-BFM 93, treated with 3 x 12 mg/m2 IDR or 6 x 30 mg/m2 daunorubicin (DNR).
Patients of the pilot study achieved a good blast cell reduction in the bone marrow on day 15, a high CR rate of 94% and a low relapse rate (3/17 pts.), however, not significantly different to the IDR (12 mg/m2) group. Hematological toxicity was high, median duration until neutrophil recovery > 500/microliter was 25.0 (12-66) days, and similar to the IDR (12 mg/m2) and DNR groups. Duration of thrombocytopenia (time to > 20,000/microliter) was 21 (10-66) days in the pilot study compared to 19 (7-26) days in DNR patients (p = 0.08). Four of 17 pilot patients presented with severe WHO grades 3/4 of mucositis during induction. One patient died in long-lasting aplasia after the 3rd treatment block.
Results of this pilot study show that the IDR 14 mg/m2 regimen was effective but also toxic. According to our results which, however, are based on small patient numbers, an improved outcome compared to the IDR 12 mg/m2 regimen seems to be unlikely, therefore the possibly increased toxicity might not be acceptable.
伊达比星（IDR）是治疗急性髓系白血病（AML）最有效的药物之一，但也具有毒性。儿童和成人诱导治疗期间的标准剂量为8 - 12mg/m²。
为改善治疗效果，在一项纳入17例患者（16例初治AML，1例继发性AML）的试点研究中，我们将诱导治疗（AIE = 阿糖胞苷、伊达比星、依托泊苷）期间3天应用的IDR剂量从12mg/m²（AML - BFM 93研究中的标准剂量）提高至14mg/m²。将结果和毒性与AML - BFM 93研究中接受3×12mg/m² IDR或6×30mg/m²柔红霉素（DNR）治疗的其他患者进行比较。
试点研究中的患者在第15天时骨髓原始细胞减少良好，完全缓解（CR）率高达94%，复发率低（3/17例患者），然而，与IDR（12mg/m²）组无显著差异。血液学毒性较高，中性粒细胞恢复至>500/微升的中位持续时间为25.0（12 - 66）天，与IDR（12mg/m²）组和DNR组相似。试点研究中血小板减少的持续时间（至>20,000/微升的时间）为21（10 - 66）天，而DNR患者为19（7 - 26）天（p = 0.08）。17例试点患者中有4例在诱导期间出现严重的WHO 3/4级黏膜炎。1例患者在第3个治疗周期后死于长期再生障碍性贫血。
这项试点研究结果表明，14mg/m² IDR方案有效但也有毒性。然而，根据我们基于小样本患者得出的结果，与12mg/m² IDR方案相比，似乎不太可能改善治疗效果，因此可能增加的毒性可能无法接受。
