Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib
Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib
复制标题
DOI：
10.1158/1078-0432.ccr-10-1359
复制
发表时间：
2011-05-15
影响因子：
11.5
通讯作者：
Dang, Chau T.
中科院分区：
文献类型：
--
作者：
Morris, Patrick G.;Chen, Carol;Dang, Chau T.
目的：目前还没有经过验证的方法来早期检测曲妥珠单抗(T)在蒽环类药物化疗后的心脏毒性。目前评估左室射血分数（LVEF）的变化，但这种方法的敏感性和特异性有限。在一项剂量密集（dd）阿霉素和环磷酰胺(AC) ->每周紫杉醇(P)与T和拉帕替尼(L)的前瞻性可行性研究中，我们包括了相关的心脏肌钙蛋白I （cTnI）和c反应蛋白（CRP）作为心脏毒性的早期生物标志物的预先计划分析。实验设计：如前所述，患者接受ddACx 4 -> PTL -> TL治疗，在化疗期间的第0、2、6、9和18个月评估LVEF，并在第6、9和18个月每2周测量cTnI和CRP。这些生物标志物与LVEF的变化相关。结果：纳入95例患者。总体而言，3例（3%）患者在AC期间退出，41例（43%）患者在PTL -> TL期间退出，主要原因是腹泻。中位LVEF为68%（基线）、69%（第2个月）、65%（第6个月）、65%（第9个月）和65%（第18个月）。在研究期间，大多数（67%）有可检测到的cTnI。可检测到的ctni比例随着时间的推移而增加；基线为4%，2个月为11%，3个月为50%。这些可检测到的ctni的时间早于LVEF的最大记录下降。然而，总体而言，最大cTnI水平与LVEF下降无关。74/95（78%）患者可检测到CRP，但与LVEF下降无关。结论：在接受ddAC -> PTL的患者中，常检测到ctni。这些升高可能先于LVEF的变化，但正如本试验评估的那样，不能预测CHF。临床癌症研究；17 (10);3490 - 9。(c) 2011年aacr。
Purpose: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) -> weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity.Experimental Design: As previously described, patients received ddACx 4 -> PTL -> TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF.Results: Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL -> TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines.Conclusion: In patients receiving ddAC -> PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF. Clin Cancer Res; 17(10); 3490-9. (C) 2011 AACR.