Saif Muhammad Wasif, Purvey Sneha, Kaley Kristin, Wasif Nawal, Carmel Annmarie, Rodriguez Teresa, Miller Kenneth B
Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra, Feinstein Institute for Medical Research, Lake Success, NY, USA.
Tufts Medical Center, Boston, MA, USA.
Eurasian J Med Oncol. 2019;3(3):182-185. doi: 10.14744/ejmo.2019.94710.
There is a wide variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs based on ethnicity. GIST is a rare cancer, (~1% of GI cancers). Imatinib is used in the neo-adjuvant, adjuvant and metastatic setting. The purpose of this study was to report the difference in hematologic toxicities to imatinib among different ethnicities when treated for GIST either in the adjuvant or metastatic setting.
We performed a retrospective study to collect data on patients with GIST (in any stage), who were on imatinib and presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenia from July 1, 2005 to January 31, 2018. The degree of cytopenia was graded as per National Cancer Institute Common Toxicity criteria; version 4.0. We collected included age, gender, ethnicity, pathology, adverse effects-hematologic and non-hematologic, management of toxicities including dose modifications and administration of pegfilgrastim.
Among 57 patients (median age 61 years, M: F=41:16 (F); ethnicities: White 65%, African-American (AA 19%, Asian 12% and Hispanic 4%), neutropenia (Grade 3 & 4) was seen in 6 patients (10%): 5 AA and 1 Asian. 45% of all AA patients developed neutropenia. Median absolute neutrophil count (ANC) nadir was 700/μL, median duration on drug prior to onset of neutropenia was 4.5 weeks and median duration of neutropenia was 4 weeks. One patient developed febrile neutropenia. Dose interruptions were needed in 3, dose-reductions in all patients, and 3 patients required pegfilgrastim. One patient had to discontinue imatinib, while one patient was escalated back to 400mg daily dose.
This is the first study to examine ethnic variations in myelosuppression following imatinib in patients with GIST.
基于种族的抗癌药物在药代动力学、药效学和耐受性方面存在很大差异。胃肠道间质瘤（GIST）是一种罕见癌症（约占胃肠道癌症的1%）。伊马替尼用于新辅助、辅助和转移性治疗。本研究的目的是报告在辅助或转移性治疗GIST时，不同种族对伊马替尼血液学毒性的差异。
我们进行了一项回顾性研究，收集2005年7月1日至2018年1月31日期间接受伊马替尼治疗且出现2级或更高级别贫血、中性粒细胞减少和/或血小板减少的GIST患者（任何阶段）的数据。细胞减少程度根据美国国立癌症研究所通用毒性标准第4.0版进行分级。我们收集的数据包括年龄、性别、种族、病理、血液学和非血液学不良反应、毒性管理（包括剂量调整和聚乙二醇化重组人粒细胞刺激因子的使用）。
57例患者（中位年龄61岁，男∶女 = 41∶16；种族：白人65%，非裔美国人19%，亚洲人12%，西班牙裔4%）中，6例（10%）出现中性粒细胞减少（3级和4级）：5例非裔美国人和1例亚洲人。所有非裔美国人患者中有45%发生中性粒细胞减少。中性粒细胞绝对计数（ANC）最低点的中位数为70 /μL，中性粒细胞减少发作前用药的中位持续时间为4.5周，中性粒细胞减少的中位持续时间为4周。1例患者发生发热性中性粒细胞减少。3例患者需要中断剂量，所有患者均需降低剂量，3例患者需要使用聚乙二醇化重组人粒细胞刺激因子。1例患者不得不停用伊马替尼，而1例患者剂量增加回每日400mg。
这是第一项研究伊马替尼治疗GIST患者后骨髓抑制种族差异的研究。
