国产去甲氧基柔红霉素治疗白血病的安全性

Multicenter randomized control trial on safety of domestic idarubicin for acute leukemia

目的探讨国产去甲氧基柔红霉素(IDA)治疗急性白血病的安全性。方法采用随机、对照、单盲的方法,155例急性白血病患者随机分入国产IDA(试验组)和进口IDA组(对照组),急性髓系白血病(AML)采用IDA 8 mg／m2,d1～3;阿糖胞苷100 mg／m2,d1～7;急性淋巴细胞白血病(ALL)IDA 8 mg／m2,d1～3;长春新碱2 mg／m2,d1;环磷酰胺750 mg／m2,d1;强的松60 mg／m2,d1～14,1～2个疗程。结果试验组和对照组的总体有效率比较,差异无统计学意义(P>0．05)。试验组和对照组出现Ⅲ-Ⅳ级骨髓抑制的发生率分别为74．0％和73．1％,两组差异无统计学意义(P= 0．73)。试验组相关死亡率为3．9％(3／77),死亡原因为脑出血和败血症。试验组和对照组的非血液学毒性发生率依次为恶心或呕吐84．4％和79．5％,感染70．1％和71．8％,口腔炎42．9％和41．0％,脱发33．8％和33．39%,转氨酶升高28．6％和28．2％,心脏毒性16．9％和10．3％,后者主要为轻度心律失常,两组差异无统计学意义(P>0．05),无因非血液学毒性停止化疗的患者。结论国产IDA联合化疗治疗急性白血病的毒性反应主要为血液学毒性,应在治疗过程中对患者密切观察和积极治疗,非血液学毒性可耐受。

Objective To evaluate the safety of domestically produced idarubicin in the treatment of acute leukemia by a muhicenter randomized control trial. Methods This trial was carried out in the hemotologica department of five hospitals throughout China, with hospitalized patients who suffered from acute myelogenous leukemia （AML except M3 type ）, acute lymphocytic leukemia （ALL）, chronic myelogenous leukemia-blast （CML-blast） , totally 155 patients. Those with severely cardial, hepatic or renal disfunction or those who had ever treated with ≥ 200 mg/m^2 idarubicin were excluded from the trial. All patients signed the letter of consent as required by the Ethics Committee of our government. In this study, 155 leukemia patients were randomly grouped into： 1. test group treated using domestic idarubicin, 2. control group using imported idarubicin. The acute myelogenous leukemia regimen included idarubicin 8 mg/m^2, d1 -3 plus cytosine arabinoside 100 mg/m^2,d1 - 7 for 1-2 cycles. The regimen for acute lymphocytic leukemia was idarubicin 8 mg/m^2 , d1 - 3 ; vincristine 2 mg/m^2 , d1 ; cyclophosphamide 750 mg/m^2 , d1 ; plus prednisone 60 mg/m^2 ,d1 - 14 for 1-2 cycles. Results Clinical response rate of the tested group treated with domestic idarubicin and control group treated with imported idarubicin was 78.1% （50/64） vs. 76.9% （50/65） without any statistically significant difference between the two groups （ P 〉 0.05 ）. Grade Ⅲ - Ⅳ hematological toxicity rate of the domestic idarubicin group and imported idarubicin group was 74.0% vs. 73.1%, respectively （P = 0.73）. Drug-related death was observed in 3 of 77 patients in the domestic idarubicin group （3.9%） due to cerebral hemorrage or septic infection. The incidence of non-hematological toxicities in domestic idarubicin group and imported idarubicin group was 84.4% vs. 79.5% for nausea or vomiting, 70.1% vs. 71.8% for infection, 42.9% vs. 41.0% for mucositis, 33.8% vs. 33.3% for alopecia, 28.6% vs. 28.2% for serum glutamicoxalacetic transaminase abnormalitis, 16.9% vs. 10.3% for cardiac toxicity, all without statistically significant differences between these two groups （ P 〉 0.05 ）. Discontinuation of treatment due to non-hematological toxicity was not neccessary. Conclusion Domestic idarubicin is comparable to imported counterpart in efficiency and safety for the treatment of acute leukemia. The most severe side effects of domestic idarubicin is hematological toxicity, which should be closely observed and treated in time, while its non-hematological toxicity is tolerable.