TREATMENT OF PATIENTS WITH LUNG CANCER

“我们研究工作的重点 在治疗肺癌的临床试验中 与肺癌的关系， 小细胞肺癌患者的回顾性分析。在 今年发表的体外研究表明，紫杉醇具有1000倍的 对非小细胞肺癌细胞系具有更强的细胞毒活性 当暴露于紫杉醇4天而不是3小时时。相位 使用4天紫杉醇联合顺铂推注剂量的I试验 显示推荐的II期剂量为120 mg/m2 紫杉醇和每平方米80毫克顺铂。的 推荐的II期剂量目前正在用于II期试验， IV期和IIIb期（伴胸腔积液）NSCLC患者， 在一项新辅助治疗试验中， 对于IIIa和IIIb期患者。三项不同的研究表明， 评估了小细胞肺癌的长期存活者， 广泛期疾病患者。一个合作的北方 来自10个机构的美国工作组确定了611 小细胞肺癌治疗后存活两年或两年以上的患者 肺癌患者中有87人患上了第二种癌症， 相对风险这主要是由于11倍的增长， 肺癌的风险。这种风险随着时间的推移而增加; 从治疗开始后2至10年增加3倍。的 这些人12年时患非小细胞肺癌的累积风险 患者为30%。胸部照射和持续吸烟 吸烟增加了患病风险。我们已经评估了 小细胞肺癌患者的预后 在过去的20年里，接受治疗的病人 近期依托泊苷顺铂加同期胸部放疗试验 比接受老年人治疗的患者稍长 基于环磷酰胺的联合治疗试验（化疗 加胸部放疗; 21个月与14个月）。而反观 广泛期小细胞肺癌患者的生存率 在过去的20年里，并没有发生重大变化。我们 广泛期小细胞肺的临床观察 在我们机构治疗的癌症促使对癌症的回顾 治疗和评估计划申办的试验，用于 广泛期小细胞肺癌这样做是为了发展 用于选择具有增加的可能性的方案的额外辅助手段 改善小细胞肺癌患者的预后。我们 确定了22项随机III期试验，用于广泛 在北美进行的小细胞肺癌分期， 1972-1993. 22项试验中有18项（82%）在以下方面没有差异： 对照组和实验组之间的存活率。其中只有4个 22项试验显示了生存率的差异。九个一期或二期 试验先于III期试验中使用的实验组。一 开发了使用患者数量的统计模型， 死亡人数，以及他们的中位生存期，以产生一个预测的 功率，通常是关于以下方面的平均统计功率 基于以下因素预期的治疗差异大小： II期临床试验和既往用药经验。中位数 II期试验的预测功效为0.39， 0.076到0.73在6项II期试验中， 随机试验中的实验组， 在III期试验中，与对照治疗相比， 0.5实验组和对照组的存活率有差异， 控制武器。这些回顾性分析的结果表明， >0.5的幂可能是在 在进入III期研究之前进行II期试验。这些数据 我认为，一个利用过去结果的统计模型， 广泛期小细胞肺癌患者的20年治疗 肺癌可以帮助预测应该采用哪些II期治疗方案 进入III期随机试验。"

"DISCONTINUED The foci of our research efforts in the treatment of lung cancer have been clinical trials for patients with lung cancer based on our in vitro experiments and retrospective analyses of patients with small cell lung cancer. In vitro studies published this year showed paclitaxel had 1000-fold more cytotoxic activity against non-small cell lung cancer cell lines when exposed to paclitaxel for 4 days rather than 3 hours. A phase I trial using 4 days of paclitaxel with a bolus dose of cisplatin showed the recommended phase II dose was 120 mg/m2 of paclitaxel and 80 mg per meter square of cisplatin. The recommended phase II dose is now being used in a phase II trial for patients with stage IV and IIIb (with pleural effusion) NSCLC and in a neoadjuvant trial combined with 6000 cGy of chest radiation for patients with stage IIIa and IIIb. Three different studies have evaluated both long-term survivors of small cell lung cancer and patients with extensive stage disease. A cooperative North American working group from 10 institutions identified 611 patients surviving two or more years after treatment for small cell lung cancer who developed 87 second cancers, a 3.5-fold increased relative risk. This was principally caused by an 11-fold increase in the risk of lung cancer. This risk increased with the passage of time; 3 fold from 2 to 10 years after the start of treatment. The cumulative risk of non-small cell lung cancer at 12 years for these patients was 30%. Chest irradiation and continued cigarette smoking contributed to the increased risk. We have evaluted the outcome of patients with small cell lung cancer treated at our institution over the last 20 years. The patients treated on the most recent etoposide cisplatin plus concurrent chest radiation trial live modestly longer than patients treated on the older cyclophosphamide-based combined modality trials (chemotherapy plus chest radiotherapy; 21 versus 14 months). In contrast, the survival of patients treated for extensive stage small cell lung cancer over the past 20 years has not changed significantly. Our observation of the patients with extensive stage small cell lung cancer treated at our institution prompted a review of the Cancer Therapy and Evaluation Program sponsored trials for patients with extensive stage small cell lung cancer. This was done to develop additional aids for selecting regimens with an increased likelihood of improved outcome for patients with small cell lung cancer. We identified 22 randomized phase III trials for patients with extensive stage small cell lung cancer performed in North America from 1972-1993. Eighteen of the 22 (82%) trials showed no difference in survival between the control and experimental arms. Only 4 of these 22 trials showed a difference in survival. Nine phase I or phase II trials preceded the experimental arms used in the phase III trials. A statistical model was developed which used the number of patients, number of deaths, and their median survival to generate a predicted power which is the usual statistical power averaged with regard to the size of the treatment difference to be expected on the basis of the phase II trial and previous experience with regimen. The median predicted power from the phase II trials was 0.39 with a range of 0.076 to 0.73. Five of the 6 phase II trials which led to the experimental arm in randomized trials which did not give longer survivals than control treatments in phase III trials had a power of 0.5 showed a difference in survival between the experimental and control arms. The results of these retrospective analyses suggest that a power of >0.5 may be a reasonable value to achieve in a phase II trial before taking it to a phase III study. These data suggest that a statistical model which utilizes the results of the past 20 years of treatment for patients with extensive stage small cell lung cancer can help predict which phase II regimens should be advanced into phase III randomized trials."