Post-Marketing Studies Management Department, Daiichi Sankyo Company Limited, 3-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo 105-8426, Japan.
Jpn J Clin Oncol. 2013 May;43(5):483-91. doi: 10.1093/jjco/hyt040. Epub 2013 Mar 27.
This analysis was conducted to clarify risk factors for severe adverse effects and treatment-related deaths reported during a postmarketing survey of irinotecan.
The survey covered all patients treated with irinotecan in Japan between April 1995 and January 2000. The patient background data and adverse drug reactions were collected through case report forms. Univariate and multivariate logistic regression analyses including 14 explanatory variables were performed to determine the risk factors for grade 3-4 leukopenia, thrombocytopenia and diarrhea for all patients and subgroups with five major cancers. Treatment-related deaths were also analyzed.
Case report forms of 13 935 patients (94.1% of 14 802 patients registered) treated with irinotecan-based chemotherapy were collected. Major grade 3-4 adverse drug reactions were leukopenia (34.8%), thrombocytopenia (12.4%) and diarrhea (10.1%). Multivariate analysis revealed that the risk factors (odds ratio ≥1.5) common for all these three adverse drug reactions were performance status (≥3), infection and renal dysfunction before starting irinotecan therapy. Additionally, the risk factors for leukopenia were being female and prior radiotherapy, those for thrombocytopenia were age (≥65 years), while those for diarrhea were pleural effusion and watery stool. The risk factors in each cancer were also identified. The incidence of treatment-related death was 1.3% (176). Myelosuppression-related deaths accounted for 70% and interstitial lung disease for 11% of all treatment-related deaths. Being male, age, performance status ≥3, massive ascites and infection and renal dysfunction were identified as risk factors for treatment-related death.
To ensure the safety of irinotecan therapy, it is important to select appropriate patients by considering the risk factors.
本分析旨在阐明伊立替康上市后监测中报告的严重不良事件和与治疗相关的死亡的风险因素。
该调查涵盖了 1995 年 4 月至 2000 年 1 月期间在日本接受伊立替康治疗的所有患者。通过病例报告表收集患者背景数据和药物不良反应。对包括 14 个解释变量的所有患者和 5 种主要癌症亚组进行单变量和多变量逻辑回归分析，以确定所有患者和 5 种主要癌症亚组中 3-4 级白细胞减少、血小板减少和腹泻的风险因素。还分析了与治疗相关的死亡。
共收集了 13935 例接受伊立替康为基础化疗的患者（登记的 14802 例患者中的 94.1%）的病例报告表。主要的 3-4 级药物不良反应为白细胞减少症（34.8%）、血小板减少症（12.4%）和腹泻（10.1%）。多变量分析显示，这三种不良反应的共同风险因素（比值比≥1.5）为开始伊立替康治疗前的体能状态（≥3）、感染和肾功能不全。此外，白细胞减少症的风险因素为女性和放疗史，血小板减少症的风险因素为年龄（≥65 岁），而腹泻的风险因素为胸腔积液和水样便。还确定了每种癌症的风险因素。治疗相关死亡的发生率为 1.3%（176 例）。骨髓抑制相关死亡占所有治疗相关死亡的 70%，间质性肺病占 11%。男性、年龄、体能状态≥3、大量腹水以及感染和肾功能不全是与治疗相关死亡的风险因素。
为确保伊立替康治疗的安全性，在考虑风险因素的情况下选择合适的患者非常重要。
