Freyer Craig W, Yaghmour George, Jennings Katherine, Dhanapal Vishnuprabha
Roswell Park Cancer Institute, Buffalo, NY, USA.
Henry Ford Hospital, Detroit, MI, USA.
J Pharm Technol. 2014 Apr;30(2):43-47. doi: 10.1177/8755122513500918. Epub 2014 Feb 28.
To report a case of drug-induced aseptic meningitis (DIAM) in a patient receiving intrathecal trastuzumab (ITT) for leptomeningeal carcinomatosis (LC) secondary to HER-2/neu positive breast cancer. A 43-year-old female with stage IV breast cancer presented with headache, parasthesias, and aphasia. Brain imaging suggested leptomeningeal enhancement. Adenocarcinoma cells were found on cerebrospinal fluid analysis, and infectious etiologies were excluded. The patient received 30 mg of ITT via Ommaya reservoir and suffered sudden neurologic deterioration within 2 hours. Given the sudden onset of clinical deterioration after ITT administration, it was determined that the patient had suffered from DIAM. The patient suffered progressive neurologic decline and was unable to care for herself any further. Treatment for LC remains challenging due to limited clinical experience and the challenging location of the disease. ITT has been used in multiple reports without adverse events. A temporal relationship existed between ITT administration and significant neurologic deterioration, possibly related to DIAM. Our patient was not exposed to any more common causative agents of DIAM. Reasons for her lack of recovery are likely multifactorial. Symptoms of DIAM may have in part been exacerbated by progressive LC; however, prior to ITT, symptoms had shown slow but persistent progression rather than significant, acute changes in severity. Retrial of the offending agent was not attempted due to patient risk; thus, a cause-and-effect relationship cannot be established. This event is a "possible" drug-induced adverse event scoring 2 on the Naranjo algorithm. Use of ITT for LC has been frequently reported in recent literature with substantial efficacy and lack of adverse events. This is the first published report of any significant adverse event associated with ITT. Clinicians need to be aware of the possibility of DIAM with ITT and explore options to prevent or manage this severe complication.
报告1例接受鞘内注射曲妥珠单抗（ITT）治疗继发于HER-2/neu阳性乳腺癌的软脑膜癌病（LC）患者发生药物性无菌性脑膜炎（DIAM）的病例。一名43岁IV期乳腺癌女性患者出现头痛、感觉异常和失语。脑部影像学检查提示软脑膜强化。脑脊液分析发现腺癌细胞，排除感染性病因。患者通过奥马亚贮器接受了30mg ITT治疗，并在2小时内突然出现神经功能恶化。鉴于ITT给药后临床恶化突然发生，确定该患者患有DIAM。患者神经功能逐渐衰退，无法再自理。由于临床经验有限且疾病位置具有挑战性，LC的治疗仍然具有挑战性。ITT已在多篇报道中使用且无不良事件。ITT给药与显著的神经功能恶化之间存在时间关系，可能与DIAM有关。我们的患者未接触任何更常见的DIAM致病因素。她未康复的原因可能是多因素的。DIAM的症状可能部分因进展性LC而加重；然而，在接受ITT之前，症状呈缓慢但持续的进展，而非严重程度的显著急性变化。由于患者风险，未尝试重新使用可疑药物；因此，因果关系无法确定。该事件是1例“可能”的药物性不良事件，根据Naranjo算法评分为2分。近期文献中频繁报道使用ITT治疗LC具有显著疗效且无不良事件。这是首篇发表的与ITT相关的任何显著不良事件的报告。临床医生需要意识到ITT导致DIAM的可能性，并探索预防或处理这种严重并发症的方法。
