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鲁比卡丁:复发性/难治性小细胞肺癌的新治疗选择。

Lurbinectedin: A New Treatment Option for Relapsed/Refractory Small-Cell Lung Cancer.

机构信息

Ascension St Vincent, Indianapolis, IN, USA.

Butler University, Indianapolis, IN, USA.

出版信息

Ann Pharmacother. 2021 Sep;55(9):1172-1179. doi: 10.1177/1060028020983014. Epub 2020 Dec 21.

DOI:10.1177/1060028020983014
PMID:33348988
Abstract

OBJECTIVE

To assess the clinical application of lurbinectedin and its role in the therapy of small-cell lung cancer (SCLC).

DATA SOURCES

PubMed database and ClincialTrials.gov were utilized to perform a comprehensive literature search from August 2011 to mid-November 2020 with the terms and .

STUDY SELECTION AND DATA EXTRACTION

English-language clinical trials of lurbinectedin were evaluated.

DATA SYNTHESIS

Lurbinectedin, as second-line therapy in SCLC, demonstrated an overall response (OR) rate of 35.2% and median overall survival of 9.3 months. Phase II studies in multiple cancers revealed myelosuppression (>95%), increased liver enzymes (>70%), nausea (up to 80%), vomiting (54%), and fatigue (>50%) as the most common adverse events associated with lurbinectedin. CYP3A4 drug interactions affect lurbinectedin exposure (severe pancytopenia occurred after coadministration with aprepitant), and protein binding can affect its clearance. Patients with cardiac comorbidities were not included in published lurbinectedin trials because of cardiotoxicity associated with trabectedin.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE

Lurbinectedin is an option in SCLC after failure of a platinum-based regimen. Dose adjustments, drug interactions, antiemetic regimen choice, and patient comorbidities are important clinical considerations with lurbinectedin use. Likewise, its place in therapy in the era of immune checkpoint inhibitors requires further exploration.

CONCLUSIONS

With a promising OR compared with other second-line options, lurbinectedin should be considered in patients who have failed first-line therapy. Studies are ongoing with lurbinectedin in combination with other agents in SCLC, and a phase III trial is assessing use in combination with doxorubicin compared with other second-line regimens.

摘要

目的

评估洛布奈丁在小细胞肺癌(SCLC)治疗中的临床应用及其作用。

数据来源

通过检索 PubMed 数据库和 ClinicalTrials.gov 数据库,以“lurbinectedin”和“small-cell lung cancer”为检索词,时间限定为 2011 年 8 月至 2020 年 11 月中旬,收集洛布奈丁治疗 SCLC 的临床研究。

研究选择和数据提取

对纳入的洛布奈丁治疗 SCLC 的临床研究进行评价。

数据综合

洛布奈丁作为 SCLC 的二线治疗药物,总缓解率(OR)为 35.2%,中位总生存期为 9.3 个月。在多种癌症的Ⅱ期研究中,洛布奈丁最常见的不良反应包括骨髓抑制(>95%)、肝酶升高(>70%)、恶心(达 80%)、呕吐(54%)和乏力(>50%)。CYP3A4 药物相互作用影响洛布奈丁的暴露,与阿瑞匹坦合用会发生严重的全血细胞减少;而蛋白结合会影响其清除率。由于与 trabectedin 相关的心脏毒性,患有心脏合并症的患者未被纳入已发表的洛布奈丁试验中。

临床意义和应用

洛布奈丁是铂类治疗失败后的 SCLC 治疗选择之一。在使用洛布奈丁时,剂量调整、药物相互作用、止吐方案选择和患者合并症等都是重要的临床考虑因素。同样,在免疫检查点抑制剂时代,它在治疗中的地位还需要进一步探索。

结论

与其他二线选择相比,OR 有较好的获益,洛布奈丁应考虑用于铂类治疗失败后的患者。目前正在进行洛布奈丁联合其他药物治疗 SCLC 的研究,一项Ⅲ期试验正在评估洛布奈丁联合多柔比星与其他二线方案的疗效比较。

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