Medical Oncology Service, Hospital Universitario Clínica Puerta de Hierro, Madrid, Spain.
Clin Lung Cancer. 2009 Jul;10(4):295-300. doi: 10.3816/CLC.2009.n.041.
Because of the poor results observed after platinum-based first-line chemotherapy, research on new strategies for second-line treatment of advanced non-small-cell lung cancer (NSCLC) is warranted. Current research focuses on the development of new agents and the assessment of a combination of therapies, especially those with different mechanisms of action. PM02734 (elisidepsin, Irvalec) is a compound related to Kahalalide F (KF), a moderately soluble marine product that belongs to a family of dehydro aminobutyric acid-containing peptides isolated from the herbivorous marine mollusk Elysia rufescens. Preclinical and clinical studies showed that KF induces strong cytotoxic activity against different solid tumors, including NSCLC, particularly in patients with squamous histology; in fact, almost 40% of patients treated in the second line were still alive at 1 year after beginning treatment with KF. Analysis of data collected during clinical development has revealed that KF has a predictable and manageable toxicity profile. The toxicities most commonly associated with KF are generally transient and mild or moderate. The absence of hematologic toxicity and cumulative toxic effects suggests that KF may be suitable for combination trials with other anticancer agents. The development of KF could stopped because of the unavailability of a natural source of the compound. PM02734 is a closely related derivative of KF with similar activity and characteristics. Herein, we summarize the studies of PM02734 and future clinical perspectives.
由于铂类药物为基础的一线化疗后观察到的效果不佳，因此有必要研究新的策略来治疗晚期非小细胞肺癌（NSCLC）的二线治疗。目前的研究重点是开发新的药物和评估联合治疗，特别是具有不同作用机制的联合治疗。PM02734（elisidepsin，Irvalec）是一种与 Kahalalide F（KF）相关的化合物，KF 是一种中等可溶性的海洋产物，属于从草食性海洋软体动物 Elysia rufescens 中分离出的一类含去氢氨基丁酸的肽。临床前和临床研究表明，KF 对不同的实体瘤具有强烈的细胞毒性活性，包括 NSCLC，尤其是鳞状组织学的患者；事实上，接受 KF 二线治疗的患者中，近 40%的患者在开始治疗 1 年后仍存活。对临床开发过程中收集的数据进行分析表明，KF 具有可预测且可管理的毒性特征。与 KF 相关的毒性通常是短暂的，轻度或中度。没有血液学毒性和累积毒性作用表明，KF 可能适合与其他抗癌药物联合试验。由于化合物的天然来源无法获得，KF 的开发已停止。PM02734 是 KF 的一种密切相关的衍生物，具有相似的活性和特征。在此，我们总结了 PM02734 的研究和未来的临床前景。
