Fischer Barbara, Arcaro Alexandre
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
Rev Recent Clin Trials. 2008 Jan;3(1):40-61. doi: 10.2174/157488708783330503.
SCLC represents 13% of all lung cancer cases and is the most aggressive form of lung cancer with an overall 5-year survival less than 5%. The combination of cisplatin or carboplatin with etoposide remains the standard treatment for SCLC. Despite a good initial response to therapy, most SCLC patients suffer from the development of chemotherapy resistance and relapse. Second-line chemotherapy should then be applied, which however frequently results in only a low survival increase. To improve the outcome of SCLC, new drugs such as topotecan, irinotecan, amrubicin, paclitaxel or gemcitabin have recently been added to chemotherapeutic regimens. In combination with etoposide or platinum-based agents, some of these drugs could be able to offer a significant survival benefit. Moreover, recent progress in the understanding of SCLC biology has led to the identification of critical signaling pathways, which allowed the development of specific targeted therapies for the disease. A number of new molecules are currently under clinical evaluation in SCLC. These inhibitors target the proteasome, receptors tyrosine kinases, farnesyltransferase, Bcl-2, or angiogenic pathways. Some studies have demonstrated that these new strategies can be associated with chemotherapy and show positive results. This review summarizes recent clinical trials performed with new chemotherapeutic regimens and the current status of specific targeted approaches in SCLC patients.
小细胞肺癌占所有肺癌病例的13%，是最具侵袭性的肺癌形式，总体5年生存率低于5%。顺铂或卡铂与依托泊苷联合使用仍然是小细胞肺癌的标准治疗方法。尽管初始治疗反应良好，但大多数小细胞肺癌患者会出现化疗耐药和复发。此时应应用二线化疗，然而这通常只会使生存率有少量提高。为了改善小细胞肺癌的治疗结果，最近拓扑替康、伊立替康、氨柔比星、紫杉醇或吉西他滨等新药已被添加到化疗方案中。其中一些药物与依托泊苷或铂类药物联合使用，可能能够带来显著的生存获益。此外，最近在小细胞肺癌生物学认识方面的进展已导致关键信号通路的识别，这使得能够开发针对该疾病的特异性靶向治疗方法。目前一些新分子正在小细胞肺癌中进行临床评估。这些抑制剂靶向蛋白酶体、受体酪氨酸激酶、法尼基转移酶、Bcl-2或血管生成途径。一些研究表明，这些新策略可以与化疗联合使用并显示出积极的结果。本综述总结了采用新化疗方案进行的近期临床试验以及小细胞肺癌患者特异性靶向治疗方法的现状。
