Singh Pritpal, Nayernama Afrouz, Christopher Jones S, Amiri Kordestani Laleh, Fedenko Katherine, Prowell Tatiana, Bersoff-Matcha Susan J
Division of Pharmacovigilance, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Division of Oncology Products, Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
J Oncol Pharm Pract. 2020 Jun;26(4):923-928. doi: 10.1177/1078155219879494. Epub 2019 Oct 8.
Docetaxel is a microtubule inhibitor indicated for the treatment of multiple cancers as a single agent or in combination with other antineoplastics. The U.S. Food and Drug Administration (FDA) conducted a postmarketing review of fatal neutropenic enterocolitis cases reported with docetaxel using the FDA Adverse Event Reporting System (FAERS) and literature to determine whether the drug was a potential cause. We searched FAERS and the literature for reports of fatal neutropenic enterocolitis with docetaxel-based treatment reported between 14 May 1996 and 13 March 2017. We characterized the clinical course and severity of neutropenic enterocolitis and utilized the World Health Organization-Uppsala Monitoring Centre rubric to assess drug causality. We identified 41 fatal cases of neutropenic enterocolitis with docetaxel from FAERS and the literature. The median time to onset of neutropenic enterocolitis from last docetaxel dose was seven days (range 2-13 days), and median time to death was nine days (range 3-23 days). The cause of death in 83% (34/41) of patients was neutropenic enterocolitis. We determined the drug-event association as probable in seven cases. Neutropenic enterocolitis with docetaxel monotherapy occurred in six cases; however, in 85% (35/41) of cases, neutropenic enterocolitis occurred when docetaxel was used in combination with other cytotoxic chemotherapy. In some cases, neutropenic enterocolitis occurred despite use of granulocyte colony-stimulating factors. Neutropenic enterocolitis is a severe and potentially fatal complication of docetaxel-based treatment, especially when combined with other antineoplastic treatments known to cause neutropenia. Practitioners should be aware of this safety risk to promptly recognize and manage patients.
多西他赛是一种微管抑制剂，可作为单一药物或与其他抗肿瘤药联合用于多种癌症的治疗。美国食品药品监督管理局（FDA）使用FDA不良事件报告系统（FAERS）和文献，对多西他赛相关的致命性中性粒细胞减少性小肠结肠炎病例进行了上市后审查，以确定该药物是否为潜在病因。我们在FAERS和文献中搜索了1996年5月14日至2017年3月13日期间报告的多西他赛治疗导致致命性中性粒细胞减少性小肠结肠炎的病例。我们对中性粒细胞减少性小肠结肠炎的临床病程和严重程度进行了描述，并利用世界卫生组织-乌普萨拉监测中心的标准评估药物因果关系。我们从FAERS和文献中确定了41例多西他赛相关的致命性中性粒细胞减少性小肠结肠炎病例。从最后一剂多西他赛给药至中性粒细胞减少性小肠结肠炎发病的中位时间为7天（范围2-13天），至死亡的中位时间为9天（范围3-23天）。83%（34/41）的患者死亡原因是中性粒细胞减少性小肠结肠炎。我们确定7例病例中药物与事件的关联很可能成立。多西他赛单药治疗发生中性粒细胞减少性小肠结肠炎6例；然而，85%（35/41）的病例中，中性粒细胞减少性小肠结肠炎发生在多西他赛与其他细胞毒性化疗联合使用时。在某些情况下，尽管使用了粒细胞集落刺激因子，仍发生了中性粒细胞减少性小肠结肠炎。中性粒细胞减少性小肠结肠炎是多西他赛治疗的一种严重且可能致命的并发症，尤其是在与其他已知可导致中性粒细胞减少的抗肿瘤治疗联合使用时。从业者应意识到这种安全风险，以便及时识别和处理患者。
