Clasen Suparna C, Ky Bonnie, O'Quinn Rupal, Giantonio Bruce, Teitelbaum Ursina, Carver Joseph R
Cardio-oncology in the Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Center for Clinical Epidemiology and Biostatistics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
J Gastrointest Oncol. 2017 Dec;8(6):970-979. doi: 10.21037/jgo.2017.09.07.
Fluoropyrimidine chemotherapy [5-fluorouracil (5-FU) and capecitabine] are commonly used agents in the treatment of various solid malignancies. However, their use has been limited by cardiac toxicity, presenting as a wide spectrum of asymptomatic (e.g., EKG changes) and symptomatic (e.g., chest pain) manifestations related to coronary vasospasm leading to myocardial ischemia. Historically, patients with suspected coronary vasospasm have been treated with traditional acute ischemic workup and various combinations of anti-anginal therapies. In addition, most patients typically are not rechallenged with fluoropyrimidine after experiencing initial cardiovascular side-effects with resulting interruption of planned chemotherapy regimens.
We report a case series of 11 consecutive patients in a single-center with suspected fluoropyrimidine-induced coronary vasospasm who were successfully rechallenged with the culprit drug to allow for planned chemotherapy completion. Our protocol utilized rechallenge with bolus infusional regimen of intravenous fluoropyrimidine chemotherapy and oral capecitabine with cardioprotective pretreatment with two calcium blockers and long-acting oral nitrate therapy.
We were successfully able to continue and complete the previously planned first-line chemotherapy regimen for all 11 patients with minimal therapeutic interruption. There have been no cardiac events or evidence of recurrent coronary spasm after completion of therapy with discontinuation of prophylactic medications upon therapy completion.
We report a single-institution experience of successful rechallenge with fluoropyrimidines with careful cardiac monitoring and the combined use of calcium channel blockers and long-acting nitrates. With further study, this algorithm can be used to safely continue fluoropyrimidines, a potentially curative regimen in the treatment of many solid tumors.
氟尿嘧啶化疗药物（5-氟尿嘧啶[5-FU]和卡培他滨）是治疗各种实体恶性肿瘤的常用药物。然而，它们的使用受到心脏毒性的限制，表现为一系列与冠状动脉痉挛导致心肌缺血相关的无症状（如心电图改变）和有症状（如胸痛）表现。从历史上看，疑似冠状动脉痉挛的患者一直采用传统的急性缺血检查和各种抗心绞痛治疗组合进行治疗。此外，大多数患者在经历初始心血管副作用导致计划化疗方案中断后，通常不会再次接受氟尿嘧啶治疗。
我们报告了一个单中心的病例系列，11例连续患者疑似氟尿嘧啶诱导的冠状动脉痉挛，他们成功地再次接受了致病药物治疗，以完成计划的化疗。我们的方案采用静脉氟尿嘧啶化疗推注方案和口服卡培他滨进行再激发，并使用两种钙通道阻滞剂进行心脏保护预处理和长效口服硝酸盐治疗。
我们成功地为所有11例患者继续并完成了先前计划的一线化疗方案，治疗中断最少。治疗完成后停止预防性用药，治疗后未发生心脏事件或复发性冠状动脉痉挛的证据。
我们报告了在严密心脏监测以及联合使用钙通道阻滞剂和长效硝酸盐的情况下，氟尿嘧啶成功再激发的单机构经验。随着进一步研究，该方案可用于安全地继续使用氟尿嘧啶，这是治疗许多实体肿瘤的一种潜在治愈方案。
