Ramanathan R K, Belani C P
Department of Medicine, University of Pittsburgh, School of Medicine, and the University of Pittsburgh Cancer Institute, PA 15213, USA.
Semin Oncol. 1997 Aug;24(4):440-54.
Until recently, chemotherapeutic intervention in advanced and metastatic non-small cell lung cancer (NSCLC) has been viewed with a certain degree of nihilism. Although meta-analysis of randomized clinical studies from the 1970s and 1980s comparing cisplatin-based chemotherapy to best supportive care in metastatic NSCLC showed improvement in survival, it was modest at best. A number of novel agents have been developed with significant activity against NSCLC in the past 5 to 6 years and are being incorporated into the therapy of this disease. These agents include paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan. Clearly there has been improvement in response rates, and in some cases the responses have been durable with an increase in the number of 1- and 2-year survivors. The next generation of studies has evaluated combinations of these novel agents with either cisplatin or carboplatin for patients with NSCLC and the results have been provocative, with 1-year survival rates as high as 54%. A randomized phase III study of the Eastern Cooperative Oncology Group has shown the superiority of paclitaxel-cisplatin regimens over etoposide-cisplatin for patients with advanced and metastatic NSCLC. The vinorelbine-cisplatin regimen has also proven to have significant, albeit modest benefit in survival when compared with cisplatin alone. These combination regimens have now become the reference regimens in ongoing randomized studies. There is continued interest in developing new agents, or selective approaches that effect novel targets with the hope of showing improved therapeutic activity. Some of these approaches include gene therapy, monoclonal antibodies, and introduction of antisense oligodeoxynucleotides. With better understanding of the molecular and cellular biology of lung cancer, the hope for the future is to combine the mechanistic approaches with new drug development to define an effective, optimal, and definitive regimen for NSCLC.
直到最近，对于晚期和转移性非小细胞肺癌（NSCLC）的化疗干预仍存在一定程度的虚无主义观点。尽管对20世纪70年代和80年代的随机临床研究进行的荟萃分析表明，在转移性NSCLC中，以顺铂为基础的化疗与最佳支持治疗相比可提高生存率，但充其量也只是适度提高。在过去5到6年中，已经开发出了多种对NSCLC具有显著活性的新型药物，并已被纳入该疾病的治疗方案中。这些药物包括紫杉醇、多西他赛、长春瑞滨、吉西他滨和伊立替康。显然，缓解率有所提高，在某些情况下，缓解持续存在，1年和2年存活者数量增加。下一代研究评估了这些新型药物与顺铂或卡铂联合用于NSCLC患者的疗效，结果令人振奋，1年生存率高达54%。东部肿瘤协作组的一项随机III期研究表明，对于晚期和转移性NSCLC患者，紫杉醇-顺铂方案优于依托泊苷-顺铂方案。与单独使用顺铂相比，长春瑞滨-顺铂方案在生存方面也已证明具有显著益处，尽管程度有限。这些联合方案现已成为正在进行的随机研究中的参考方案。人们持续对开发新药物或针对新靶点的选择性方法感兴趣，希望能展现出更好的治疗活性。其中一些方法包括基因治疗、单克隆抗体和反义寡脱氧核苷酸的应用。随着对肺癌分子和细胞生物学的深入了解，未来的希望是将机制性方法与新药开发相结合，为NSCLC确定一种有效、最佳且明确的治疗方案。
