Socinski M A, Shea T C
Multidisciplinary Thoracic Oncology Program, Department of Medicine, University of North Carolina at Chapel Hill, USA.
Semin Oncol. 1997 Aug;24(4 Suppl 12):S12-45-S12-51.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer deaths in the United States. The combination of more active agents like vinorelbine and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with cisplatin has led to improved survival for patients with advanced metastatic disease. The ability to escalate the dose of cisplatin-based regimens is limited by nonhematologic toxicities and is especially difficult in the population of patients with advanced NSCLC. However, the development of new agents with significant activity against NSCLC as well as new strategies for high-dose therapy have made it possible to examine the potential of dose-intense therapy in this population. A phase I trial performed at the University of North Carolina was designed to evaluate paclitaxel 250 mg/m2 given over 24 hours plus escalating doses of carboplatin starting at an area under the concentration-time curve (AUC) dose of 8 supported by peripheral blood stem cells and filgrastim in the treatment of advanced NSCLC. The AUC dose of carboplatin was escalated in increments of 2. The maximum tolerated dose of carboplatin combined with paclitaxel 250 mg/m2 administered over 24 hours was defined at an AUC of 18. In this study, six of seven patients with advanced NSCLC had major responses. This regimen is currently being tested in patients with locally advanced NSCLC by the Cancer and Leukemia Group B: patients receive two cycles of induction therapy with paclitaxel 250 mg/m2 over 3 hours followed by carboplatin at an AUC of 18 supported by peripheral blood stem cells and filgrastim. Depending on response to induction therapy, patients then receive surgical resection, thoracic radiation therapy, or both. This phase II trial will examine clinical and pathologic responses and the toxicity of this high-dose regimen in patients with locally advanced NSCLC. Ultimately, phase III trials will be needed to establish the role of this approach in NSCLC.
非小细胞肺癌（NSCLC）仍是美国癌症死亡的主要原因。长春瑞滨和紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）等更具活性的药物与顺铂联合使用，已使晚期转移性疾病患者的生存率得到提高。基于顺铂的治疗方案增加剂量的能力受到非血液学毒性的限制，在晚期NSCLC患者群体中尤其困难。然而，具有显著抗NSCLC活性的新型药物的开发以及高剂量治疗的新策略，使得研究该群体中剂量密集治疗的潜力成为可能。在北卡罗来纳大学进行的一项I期试验旨在评估在24小时内给予250 mg/m²紫杉醇，加用从浓度-时间曲线下面积（AUC）剂量8开始递增的卡铂剂量，并辅以外周血干细胞和非格司亭，用于治疗晚期NSCLC。卡铂的AUC剂量以2的增量递增。卡铂与24小时内给予的250 mg/m²紫杉醇联合使用的最大耐受剂量定义为AUC 18。在本研究中，7例晚期NSCLC患者中有6例有主要反应。癌症与白血病B组目前正在局部晚期NSCLC患者中对该方案进行测试：患者接受两个周期的诱导治疗，3小时内给予250 mg/m²紫杉醇，随后给予AUC为18的卡铂，并辅以外周血干细胞和非格司亭。根据诱导治疗的反应，患者随后接受手术切除、胸部放射治疗或两者兼而有之。这项II期试验将研究该高剂量方案在局部晚期NSCLC患者中的临床和病理反应以及毒性。最终，需要进行III期试验来确定这种方法在NSCLC中的作用。
