Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Clin Cancer Res. 2011 May 15;17(10):3490-9. doi: 10.1158/1078-0432.CCR-10-1359. Epub 2011 Mar 3.
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.
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.
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.
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.
在蒽环类化疗后曲妥珠单抗（T）引起的心脏毒性，目前还没有经过验证的早期检测方法。目前评估左心室射血分数（LVEF）的变化，但这种方法的敏感性和特异性有限。在密集剂量（dd）多柔比星和环磷酰胺（AC）→每周紫杉醇（P）联合 T 和拉帕替尼（L）的前瞻性可行性研究中，我们包括了一个预先计划的分析，即心脏肌钙蛋白 I（cTnI）和 C 反应蛋白（CRP）作为心脏毒性的早期生物标志物。
如前所述，患者接受 ddACx4→PTL→TL。在 0、2、6、9 和 18 个月评估 LVEF，并在化疗期间每 2 周测量 cTnI 和 CRP，然后在 6、9 和 18 个月时测量。这些生物标志物与 LVEF 的变化相关。
95 例患者入组。总的来说，在 AC 期间有 3 例（3%）患者退出，在 PTL→TL 期间有 41 例（43%）患者退出，主要是由于腹泻。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）。大多数患者（67%）在研究期间检测到 cTnI。检测到的 cTnI 比例随时间增加；基线时为 4%，第 2 个月时为 11%，第 3 个月时为 50%。这些可检测到的 cTnI 的时间先于 LVEF 记录到的最大下降。然而，总的来说，最大 cTnI 水平与 LVEF 下降无关。95 例患者中有 74 例（78%）检测到 CRP，但与 LVEF 下降无关。
在接受 ddAC→PTL 的患者中，cTnI 通常被检测到。这些升高可能先于 LVEF 的变化，但在本试验中评估，并不预测 CHF。
