Lustberg Maryam B, Edelman Martin J
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Curr Treat Options Oncol. 2007 Feb;8(1):38-46. doi: 10.1007/s11864-007-0020-6.
NSCLC is the leading cause of cancer mortality in the United States. Approximately 30-40% of patients present with advanced stage disease (Stage IIIb with malignant effusion and Stage IV) and the majority of those who present with "earlier" disease will ultimately develop and succumb to metastatic lung cancer. Although platinum-based combination chemotherapy has been shown to impact overall survival and quality of life, it is not curative and less than 25% of patients survive 2 years. Therefore, the benefits of chemotherapy must be weighed against toxicity, inconvenience, and cost. Several randomized trials have shown that there is no added benefit of extending first line, platinum-based chemotherapy beyond four cycles. There was no additional survival benefit and patients experienced increased toxicity with longer durations of therapy. Attempts to improve outcome by planned sequential therapy, i.e. shifting from one cytotoxic regimen to another after a fixed number of cycles have also not been successful. Several new so-called "targeted" therapeutic agents have recently been evaluated in clinical trials to assess whether the efficacy of first line chemotherapy with platinum doublets can be improved with the addition of these agents. These include bevacizumab, epidermal growth factor receptor inhibitors (erlotinib and gefitinib), bexarotene, matrix metalloproteinase inhibitors, and others. Other than bevacizumab, none have demonstrated benefit in this scenario. The design of most of these trials employed the concurrent use of the new agent with six cycles of platinum-based chemotherapy (usually either carboplatin/paclitaxel or cisplatin/gemcitabine) and then continued the new agent until relapse. Three agents have demonstrated benefit in randomized studies in the second line setting, docetaxel, pemetrexed, and erlotinib. No study has evaluated the optimal duration of therapy for these agents, though for erlotinib, it appears that use until progression is optimal. Future studies of novel agents will need to explore not only the potential use of these agents in combination or in comparison with standard therapy, but also the duration of therapy and consider issues of survival, quality of life, and cost.
非小细胞肺癌（NSCLC）是美国癌症死亡的主要原因。约30%-40%的患者就诊时已处于晚期疾病阶段（伴有恶性胸腔积液的Ⅲb期和Ⅳ期），而大多数就诊时处于“早期”疾病阶段的患者最终会发展为转移性肺癌并死亡。尽管铂类联合化疗已被证明可影响总生存期和生活质量，但它并非根治性疗法，不到25%的患者能存活2年。因此，必须权衡化疗的益处与毒性、不便之处及成本。多项随机试验表明，将一线铂类化疗延长至四个周期以上并无额外益处。没有额外的生存获益，且随着治疗时间延长患者毒性增加。通过计划性序贯治疗来改善结局的尝试，即在固定周期数后从一种细胞毒性方案转换为另一种方案，也未成功。最近在临床试验中评估了几种新的所谓“靶向”治疗药物，以确定在铂类双联方案一线化疗中添加这些药物是否能提高疗效。这些药物包括贝伐单抗、表皮生长因子受体抑制剂（厄洛替尼和吉非替尼）、贝沙罗汀、基质金属蛋白酶抑制剂等。除贝伐单抗外，在这种情况下均未显示出益处。这些试验大多设计为将新药与六个周期的铂类化疗（通常为卡铂/紫杉醇或顺铂/吉西他滨）同时使用，然后继续使用新药直至复发。三种药物在二线治疗的随机研究中显示出益处，即多西他赛、培美曲塞和厄洛替尼。尚无研究评估这些药物的最佳治疗持续时间，不过对于厄洛替尼，似乎持续使用至病情进展是最佳的。未来新型药物的研究不仅需要探索这些药物联合使用或与标准治疗比较的潜在用途，还需要考虑治疗持续时间，并兼顾生存、生活质量和成本等问题。
