Schöber C, Papageorgiou E, Harstrick A, Bokemeyer C, Mügge A, Stahl M, Wilke H, Poliwoda H, Hiddemann W, Köhne-Wömpner C H
Department of Hematology/Oncology, University Medical School, Hannover, Germany.
Cancer. 1993 Oct 1;72(7):2242-7. doi: 10.1002/1097-0142(19931001)72:7<2242::aid-cncr2820720730>3.0.co;2-e.
Cardiotoxicity related to the widely used cytotoxic compound 5-fluorouracil (5-FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5-FU and folinic acid.
The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate-dose folinic acid and 5-FU was reviewed.
The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5-FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2-6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect.
Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5-FU and leucovorin does not differ from single-agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.
与广泛使用的细胞毒性化合物5-氟尿嘧啶（5-FU）相关的心脏毒性与使用蒽环类药物时观察到的频率相比罕见。包含活性生物调节化合物如亚叶酸（FA）的更有效方案或联合化疗也会改变毒性的类型和严重程度。本研究的目的是评估5-FU与亚叶酸联合使用时的心脏毒性。
回顾了作者对390例接受中剂量亚叶酸和5-FU治疗晚期胃肠道癌患者的多中心经验。
心脏毒性的总体风险为3%，并不显著高于单独使用5-FU时报告的风险。53例有心脏病史的患者中有8例报告有心脏症状（15.1%），相比之下，337例无心脏病史的患者中有5例（1.5%）有心脏症状。出现症状的中位时间为3天（范围为2 - 6天）。9例患者有类似心肌缺血的症状，1例患者因推测与氟尿嘧啶治疗密切相关的心肌梗死死亡，4例患者有室上性心律失常，1例患者有充血性心力衰竭。心脏病史是与心脏毒性相关的唯一危险因素。尽管前一周期有心脏症状，但再次治疗时复发频繁。治疗性或预防性给予硝酸盐无显著效果。
医生应了解活性氟尿嘧啶治疗的心脏毒性特性。5-FU与亚叶酸联合使用在心脏毒性的频率或类型上与单药治疗无差异。必须密切监测患者，尤其是那些有心脏副作用高风险的患者。如果出现冠状动脉症状应停止治疗，因为对此类症状既没有有效的治疗方法也没有预防措施。
