Dómine Gómez Manuel, Subbiah Vivek, Peters Solange, Sala María Angeles, Trigo José, Paz-Ares Luis, Nieto Archilla Antonio, Gomez Garcia Javier, Alvarez García Cristina, López-Vilariño de Ramos José Antonio, Kahatt Lopez Carmen, Fernandez Cristian M
Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Universidad Autónoma de Madrid, Madrid, Spain.
Early-Phase Drug Development, Sarah Cannon Research Institute, Nashville, TN, USA.
Expert Rev Anticancer Ther. 2025 Jan;25(1):27-40. doi: 10.1080/14737140.2024.2438067. Epub 2024 Dec 12.
Platinum rechallenge is recommended for patients with small cell lung cancer (SCLC) who relapse ≥90 days after completing first-line chemotherapy, although it may not always be the most suitable option.
Articles for review were identified via PubMed and ClinicalTrials.gov searches, supplemented with non-indexed publications (e.g. conference abstracts) known to the manufacturer. We examined evidence for platinum re-exposure in patients with sensitive relapsed SCLC, and present lurbinectedin as a potential alternative. The complementary mechanisms of action of lurbinectedin and platinum, owing to opposite sensitivity of SCLC cells, may resensitize tumor cells to platinum. As efficacy outcomes with lurbinectedin are equivalent or better than those with platinum rechallenge and its hematological safety profile is more favorable, achieving maximum dose intensity is more likely. The simpler dosing schedule of lurbinectedin (1 vs 3 days) and lack of need for granulocyte colony-stimulating factor primary prophylaxis lessens treatment burden.
Incorporation of lurbinectedin into therapeutic algorithms for relapsed SCLC has challenged long-established treatment paradigms. Initial evidence indicates that using lurbinectedin after failure of first-line platinum may prolong the platinum-free interval and reserve platinum for later use. Current evidence supports lurbinectedin as a second-line option in patients with sensitive relapsed SCLC.
对于在完成一线化疗后≥90天复发的小细胞肺癌(SCLC)患者,推荐进行铂类再挑战治疗,尽管这可能并不总是最合适的选择。
通过PubMed和ClinicalTrials.gov检索确定用于综述的文章,并补充制造商已知的非索引出版物(如会议摘要)。我们研究了敏感复发SCLC患者铂类再暴露的证据,并介绍了鲁比卡丁作为一种潜在的替代方案。由于SCLC细胞的敏感性相反,鲁比卡丁和铂类的互补作用机制可能使肿瘤细胞对铂类重新敏感。由于鲁比卡丁的疗效结果与铂类再挑战相当或更好,且其血液学安全性更有利,因此更有可能实现最大剂量强度。鲁比卡丁更简单的给药方案(1天与3天)以及无需粒细胞集落刺激因子初级预防减轻了治疗负担。
将鲁比卡丁纳入复发SCLC的治疗方案挑战了长期确立的治疗模式。初步证据表明,在一线铂类治疗失败后使用鲁比卡丁可能会延长无铂间期,并保留铂类以供后续使用。目前的证据支持鲁比卡丁作为敏感复发SCLC患者的二线选择。