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成人癌症患者接受细胞毒化疗后的血小板减少症:一项回顾性基于医院的队列研究结果。

Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.

机构信息

Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.

出版信息

Drug Saf. 2011 Dec 1;34(12):1151-60. doi: 10.2165/11594310-000000000-00000.

Abstract

BACKGROUND

Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited.

OBJECTIVE

The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment.

METHODS

For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents.

RESULTS

A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%).

CONCLUSIONS

The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient.

摘要

背景

在临床实践中,接受化疗的实体瘤患者的化疗诱导性血小板减少症(CIT)的频率和相对风险(RR)的数据有限。

目的

本研究旨在评估接受化疗的成年实体瘤患者发生血小板减少症的频率和 RR。

方法

对于这项回顾性的基于医院的研究,我们从乌得勒支患者导向数据库中确定了 2004 年至 2006 年期间在乌得勒支大学医学中心接受化疗的成年实体瘤患者。我们检查了以下情况的频率:(i)总体血小板减少症(定义为血小板计数<100×109/L)伴或不伴其他血细胞减少症;(ii)单纯血小板减少症(即无其他血细胞减少症);以及(iii)不同细胞毒药物相关的总体血小板减少症和单纯血小板减少症的频率和 RR。

结果

共纳入 614 名接受 37 种不同化疗方案之一的患者。总体血小板减少症的发生率为 21.8%,单纯血小板减少症的发生率为 6.2%。接受卡铂单药治疗(81.8%)和包含卡铂(58.2%)、吉西他滨(64.4%)或紫杉醇(59.3%)的联合治疗的患者血小板减少症发生率最高。与顺铂为基础的治疗相比,血小板减少症的 RR 最高的是卡铂/吉西他滨(RR 10.1;95%CI 5.5,18.5)和卡铂/紫杉醇/依托泊苷(RR 11.8;95%CI 6.7,20.8)的联合治疗。在 54%的病例中,血小板减少症为 2-4 级,这被认为是最具临床意义的等级。观察到的单纯血小板减少症发生率最高的是包含奥沙利铂(28.6%)或吉西他滨(28.9%)的联合治疗。

结论

结果表明 CIT 在临床实践中是一个相关的问题。需要进一步研究以调查血小板减少症的临床后果。观察到的血小板减少症频率低于旧研究,但与最近的一项美国研究相似。观察到的与接触奥沙利铂和吉西他滨相关的可能免疫介导性血小板减少症的风险增加,提示这些药物可能导致免疫介导性血小板减少症,需要进一步研究。对于临床医生来说,该机制具有重要的意义,因为在免疫介导性血小板减少症中必须避免使用药物,而在剂量依赖性血小板减少症中,减少剂量可能就足够了。

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