ICRF-187 permits longer treatment with doxorubicin in women with breast cancer.
ICRF-187 permits longer treatment with doxorubicin in women with breast cancer.
复制标题
ICRF-187 允许对患有乳腺癌的女性进行更长时间的阿霉素治疗。
DOI：
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发表时间：
1992
影响因子：
45.3
通讯作者：
M. Meyers
中科院分区：
文献类型：
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作者：
J. Speyer;Michael D. Green;A. Zeleniuch‐Jacquotte;Wernz Jc;M. Rey;J. Sanger;E. Kramer;V. Ferrans;H. Hochster;M. Meyers
目的
为了测试ICRF - 187对阿霉素累积剂量相关心脏毒性的潜在保护作用，我们在150名晚期乳腺癌女性患者中进行了一项随机临床试验。
患者与方法
患者每21天静脉注射（IV）氟尿嘧啶（5FU）500 mg/m²、阿霉素50 mg/m²和环磷酰胺500 mg/m²（对照组，74名患者），或者在注射相同药物组合之前先静脉注射ICRF - 187 1000 mg/m²（试验组，76名患者）。
结果
我们之前报道过，在此剂量和疗程下，ICRF - 187可提供心脏保护作用，且不会显著改变对照组方案的非心脏毒性或抗肿瘤疗效。在对整个患者队列的此次更新分析中，我们为这些发现提供了更多支持，并证明ICRF - 187组患者接受的阿霉素周期数（中位数为11）和累积剂量（中位数为500 mg/m²）均高于对照组患者（中位数为9个周期，P < 0.01；441 mg/m²，P < 0.05）。ICRF - 187组中有26名患者接受的阿霉素剂量至少为700 mg/m²，其中11名患者接受了1000 mg/m²或更高剂量。对照组中只有3名患者接受的阿霉素剂量为700 mg/m²；该组中一名患者接受的最大剂量为950 mg/m²。通过临床充血性心力衰竭（CHF）的发生率差异（ICRF - 187组2名患者，对照组20名患者；P < 0.0001）以及通过多门控放射性核素（MUGA）扫描测定的静息左心室射血分数（LVEF）与基线的差异以及因该差异需将患者从研究中剔除的情况（ICRF - 187组有5名患者LVEF降至小于0.45或较基线LVEF降低0.20或更多，对照组32名患者；P < 0.000001），证明了ICRF - 187的心脏保护作用。在累积阿霉素剂量达到450 mg/m²时进行了心内膜心肌活检且结果可评估的30名患者中，ICRF - 187组的16名患者中无一人评分达到2分，而对照组的14名患者中有6人评分达到2分（P < 0.05）。在有和没有既往胸壁放疗或其他阿霉素心脏毒性风险因素的患者中均观察到了ICRF - 187的心脏保护作用。
结论
通过预防阿霉素累积诱导的心脏毒性，ICRF - 187能让患者更安全地接受剂量显著更高的阿霉素。
PURPOSE
To test potential protection by ICRF-187 against cumulative doxorubicin-dose-related cardiac toxicity, we conducted a randomized clinical trial in 150 women with advanced breast cancer.
PATIENTS AND METHODS
Patients received fluorouracil (5FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days intravenously (IV) (control regimen, 74 patients), or the same regimen preceded by ICRF-187 1,000 mg/m2 IV (experimental regimen, 76 patients).
RESULTS
We previously reported that ICRF-187 in this dose and schedule provides cardiac protection and does not substantially alter the noncardiac toxicity or antitumor efficacy of the control regimen. In this updated analysis of the entire patient cohort, we provide additional support for these findings and demonstrate that patients in the ICRF-187 group received more cycles (median, 11) and higher cumulative doses (median, 500 mg/m2) of doxorubicin than patients in the control group (median, nine cycles, P less than .01; and 441 mg/m2, P less than .05). Twenty-six patients in the ICRF-187 group received doxorubicin doses of at least 700 mg/m2, and among them, 11 patients received 1,000 mg/m2 or more. Only three patients in the control group received doxorubicin doses of 700 mg/m2; the maximum dose administered to one patient in this group was 950 mg/m2. ICRF-187 cardiac protection was demonstrated by difference in incidence of clinical congestive heart failure (CHF; two patients in the ICRF-187 group v 20 in the control group; P less than .0001) and by differences in resting left ventricular ejection fraction (LVEF) determined by multigated radionuclide (MUGA) scan from baselines and that required patient removal from study (five patients in the ICRF-187 group had a decrease in LVEF to less than 0.45 or a decrease from the baseline LVEF of 0.20 or more v 32 in the control group; P less than .000001). Among the 30 patients who had an assessable endomyocardial biopsy at cumulative doxorubicin 450 mg/m2, none of 16 in the ICRF-187 group and six of 14 in the control group had a score of 2 (P less than .05). ICRF-187 cardiac protection was observed in patients with and without prior chest-wall radiation or other risk factors for developing doxorubicin cardiac toxicity.
CONCLUSION
By protecting against cumulative doxorubicin-induced cardiac toxicity, ICRF-187 permits significantly greater doses of doxorubicin to be administered to patients with greater safety.
影响因子：
158.5
作者：
LIPSHULTZ, SE;COLAN, SD;SANDERS, SP
通讯作者：
SANDERS, SP