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奥沙利铂诱导的肝细胞损伤和耳毒性:文献综述及一种常用化疗药物罕见副作用报告

Oxaliplatin-induced hepatocellular injury and ototoxicity: a review of the literature and report of unusual side effects of a commonly used chemotherapeutic agent.

作者信息

Vietor Nicole O, George Benjamin J

机构信息

Department of Internal Medicine, Brooke Army Medical Center, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, TX 78234, USA.

出版信息

J Oncol Pharm Pract. 2012 Sep;18(3):355-9. doi: 10.1177/1078155212437901. Epub 2012 Feb 14.

DOI:10.1177/1078155212437901
PMID:22333669
Abstract

After extensive literature review utilizing PubMed and Medline searches, we present a rare case of oxaliplatin-induced grade 3/4 hepatocellular injury and ototoxicity. The patient is a 46-year-old female diagnosed with stage IIIC (pT3N2bM0) adenocarcinoma of the sigmoid colon. PET/CT prior to surgery and chemotherapy was negative for distant metastatic disease and baseline liver-associated enzymes were within normal limits. Following sigmoidectomy, patient began adjuvant chemotherapy with 5-florouracil, leucovorin, and oxaliplatin (mFOLFOX-6). Cycle 1 was complicated only by refractory nausea. However, cycle 2 was complicated by vertigo with refractory nausea, tinnitus, and marked elevation in liver enzymes in a hepatocellular pattern. Extensive workup was negative and the etiology of her symptoms and grade 3/4 hepatocellular injury was hypothesized to be the result of oxaliplatin. Aspartate aminotransferase and alanine aminotransferase decreased after two additional weeks off therapy and during cycle 3 in which oxaliplatin was held. She had no evidence of 5-florouracil toxicity. On cycle 4, oxaliplatin was restarted at 50% dose; symptoms and liver-associated enzymes remained stable. However, oxaliplatin was increased up to 75% full dose for cycle 5 with reported vertigo, tinnitus, nausea, and return of elevation in liver-associated enzymes. Oxaliplatin is a chemotherapy agent widely used in the treatment of many malignancies including colon cancer. Side effects include peripheral neuropathy, gastrointestinal toxicity, neutropenia, grade 1/2 hepatocellular injury, and hepatic vascular lesions. However, grade 3/4 hepatocellular injury and ototoxicity are extremely rare with the administration of oxaliplatin. Therefore, we present the unusual chemotherapy side effects.

摘要

在利用PubMed和Medline搜索进行广泛的文献综述后,我们报告了一例罕见的奥沙利铂引起的3/4级肝细胞损伤和耳毒性病例。患者为一名46岁女性,被诊断为乙状结肠癌IIIC期(pT3N2bM0)腺癌。手术和化疗前的PET/CT检查未发现远处转移疾病,基线肝相关酶在正常范围内。乙状结肠切除术后,患者开始接受5-氟尿嘧啶、亚叶酸钙和奥沙利铂(mFOLFOX-6)辅助化疗。第1周期仅出现难治性恶心的并发症。然而,第2周期出现眩晕并伴有难治性恶心、耳鸣,且肝细胞型肝酶显著升高。广泛检查均为阴性,推测其症状和3/4级肝细胞损伤的病因是奥沙利铂。在停药两周并在第3周期停用奥沙利铂后,天冬氨酸转氨酶和丙氨酸转氨酶下降。她没有5-氟尿嘧啶毒性的证据。在第4周期,奥沙利铂以50%剂量重新开始使用;症状和肝相关酶保持稳定。然而,在第5周期奥沙利铂剂量增加至75%全剂量时,出现了眩晕、耳鸣、恶心,肝相关酶再次升高。奥沙利铂是一种广泛用于治疗包括结肠癌在内的多种恶性肿瘤的化疗药物。其副作用包括周围神经病变、胃肠道毒性、中性粒细胞减少、1/2级肝细胞损伤和肝血管病变。然而,使用奥沙利铂时出现3/4级肝细胞损伤和耳毒性极为罕见。因此,我们报告了这种不寻常的化疗副作用。

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