Lehmann D F, Hurteau T E, Newman N, Coyle T E
Department of Medicine, School of Medicine, State University of New York Health Science Center at Syracuse 13210, USA.
Clin Pharmacol Ther. 1997 Aug;62(2):225-9. doi: 10.1016/S0009-9236(97)90071-0.
Procarbazine usage in brain tumors has a high incidence of hypersensitivity reactions compared with its use in other malignancies. Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital. Patients with primary brain tumors would have a preferential exposure to anticonvulsants compared to patients with other malignancies.
To determine whether anticonvulsant exposure is associated with procarbazine hypersensitivity reactions in patients with primary brain tumors.
This retrospective cohort study included 83 patients with primary brain tumors who were treated with procarbazine between 1981 and 1996 at a university hospital-based regional oncology center. Data were extracted by chart review. The data collected included age, sex, race, tumor type, smoking, alcohol usage, and all concomitant medications, as well as creatinine, aspartate aminotransferase, total bilirubin, and anticonvulsant serum levels. Anticonvulsant exposure was determined by the presence of detectable serum levels. Cases of procarbazine hypersensitivity reactions were identified through a review of progress notes.
There were 20 patients with procarbazine hypersensitivity reactions. A significant association between the exposure to anticonvulsants and the development of procarbazine hypersensitivity reactions was found (p = 0.05). In addition, there was a significant dose-response association between the development of procarbazine hypersensitivity and the presence of therapeutic anticonvulsant serum levels (p = 0.03).
Concomitant exposure to anticonvulsants is associated with procarbazine hypersensitivity reactions, possibly though a reactive intermediate generated by CYP3A isoform induction. All patients in this cohort received enzyme-inducing anticonvulsants. New anticonvulsants devoid of this property are available. These data support trials that use these newer agents for the prophylaxis of seizures in patients with brain tumors who are to receive procarbazine.
与用于其他恶性肿瘤相比，丙卡巴肼用于脑肿瘤时超敏反应的发生率较高。苯巴比妥可增强丙卡巴肼氧化为活性中间体的过程。与其他恶性肿瘤患者相比，原发性脑肿瘤患者更易接触抗惊厥药。
确定抗惊厥药暴露与原发性脑肿瘤患者丙卡巴肼超敏反应是否相关。
这项回顾性队列研究纳入了1981年至1996年在一家大学医院附属地区肿瘤中心接受丙卡巴肼治疗的83例原发性脑肿瘤患者。通过查阅病历提取数据。收集的数据包括年龄、性别、种族、肿瘤类型、吸烟、饮酒情况以及所有合并用药，还有肌酐、天冬氨酸转氨酶、总胆红素和抗惊厥药血清水平。通过可检测到的血清水平来确定抗惊厥药暴露情况。通过查阅病程记录确定丙卡巴肼超敏反应病例。
有20例患者发生丙卡巴肼超敏反应。发现抗惊厥药暴露与丙卡巴肼超敏反应的发生之间存在显著关联（p = 0.05）。此外，丙卡巴肼超敏反应的发生与治疗性抗惊厥药血清水平的存在之间存在显著的剂量反应关联（p = 0.03）。
同时暴露于抗惊厥药与丙卡巴肼超敏反应相关，可能是通过CYP3A同工酶诱导产生的活性中间体介导。该队列中的所有患者均接受了诱导酶的抗惊厥药。有不具有此特性的新型抗惊厥药。这些数据支持在接受丙卡巴肼治疗的脑肿瘤患者中使用这些新型药物预防癫痫发作的试验。
