Ekstein Sivan, Nir Amiram, Rein Azaria J J T, Perles Zeev, Bar-Oz Benjamin, Salpeter Lea, Algur Nurit, Weintraub Michael
Department of Pediatrics, Shaare-Zedek Medical Center, Jerusalem, Israel.
J Pediatr Hematol Oncol. 2007 Jul;29(7):440-4. doi: 10.1097/MPH.0b013e3180640d42.
Anthracyclines are widely used in the treatment of pediatric cancer but their use is associated with cardiotoxicity. The cardiotoxic effect may become clinically apparent many years after therapy, and no reliable method exists for early detection of cardiac damage while the patient is receiving the drug. The natriuretic peptides have been established as markers for anthracycline-induced cardiotoxicity in adults and markers for cardiac dysfunction in children. We examined whether N-terminal proB-type natriuretic peptide (NT-proBNP) may be used as a marker for anthracycline-induced cardiotoxicity in children.
Twenty-three consecutive pediatric patients with newly diagnosed cancer were enrolled in this study. All patients received anthracycline-containing chemotherapy. Fifty-four age-matched children served as controls. Serial measurements of plasma NT-proBNP levels were taken before and after each anthracycline-containing course. Echocardiograms were performed before initiation of treatment and at the end of the study.
Plasma levels of NT-proBNP were within normal limits before treatment and increased significantly only after the first anthracycline dose (from 150+/-112 to 327+/-321 pg/mL, mean+/-SD, P=0.02) and not after subsequent doses. This increase was attributed mainly to a subgroup of patients who received more than 25 mg/m of doxorubicin. In 14 patients (61%), the highest NT-proBNP level occurred after the first anthracycline dose. All patients had normal echocardiograms and none developed heart failure.
NT-proBNP increases significantly after the first anthracycline course in a subset of pediatric cancer patients. This increase is not associated with clinical or echocardiographic evidence of cardiac dysfunction. Anthracyclines may be more cardiotoxic in the first course than in subsequent courses. Longer follow-up of these patients is necessary to determine whether NT-proBNP can be used as an early marker for anthracycline-induced cardiotoxicity.
蒽环类药物广泛应用于儿童癌症的治疗,但其使用与心脏毒性有关。心脏毒性作用可能在治疗多年后才在临床上显现出来,而且在患者接受药物治疗期间,尚无可靠的方法可早期检测心脏损伤。利钠肽已被确立为成人蒽环类药物所致心脏毒性的标志物以及儿童心脏功能障碍的标志物。我们研究了N末端B型利钠肽原(NT-proBNP)是否可作为儿童蒽环类药物所致心脏毒性的标志物。
本研究纳入了23例新诊断癌症的连续儿科患者。所有患者均接受含蒽环类药物的化疗。54例年龄匹配的儿童作为对照。在每个含蒽环类药物疗程前后,对血浆NT-proBNP水平进行连续测量。在治疗开始前和研究结束时进行超声心动图检查。
治疗前血浆NT-proBNP水平在正常范围内,仅在首次给予蒽环类药物剂量后显著升高(从150±112 pg/mL升至327±321 pg/mL,均值±标准差,P = 0.02),后续剂量后未升高。这种升高主要归因于接受多柔比星超过25 mg/m²的患者亚组。在14例患者(61%)中,NT-proBNP最高水平出现在首次给予蒽环类药物剂量后。所有患者超声心动图均正常,且无患者发生心力衰竭。
在一部分儿科癌症患者中,首次蒽环类药物疗程后NT-proBNP显著升高。这种升高与心脏功能障碍的临床或超声心动图证据无关。蒽环类药物在首个疗程可能比后续疗程更具心脏毒性。需要对这些患者进行更长时间的随访,以确定NT-proBNP是否可作为蒽环类药物所致心脏毒性的早期标志物。