TREATMENT OF PATIENTS WITH LUNG CANCER

肺癌生物学组研究了延长的影响

The Lung Cancer Biology Section has studied the effect of prolonged exposure of paclitaxel to lung cancer and the rate of developing second cancers in a large North American cohort of patients surviving small cell lung cancer. Twenty-eight lung cancer cell lines were studied with increasing durations of exposure to paclitaxel. The median paclitaxel concentration required to inhibit 50% of the growth of 14 non-small cell lung cancer (NSCLC) cell lines measured by MTT assay decreased more than 1000-fold when the exposure duration increased from 3 to 120 hours. The median paclitaxel concentration required to inhibit 50% of the cell growth of SCLC cell lines decreased 10-fold when the exposure duration increased from 3 to 120 hours. Based on this in vitro, we performed a phase I trial of a 96 hour infusion of paclitaxel followed by cisplatin. Fifty patients with previously untreated lung cancer (42 with NSCLC and 8 with SCLC) were treated with increasing doses of paclitaxel administered as a 96 hour infusion followed by increasing doses of cisplatin. The recommended phase II dose was 120 mg/m of paclitaxel and 80 mg per meter squared of cisplatin. The dose limiting toxicity was hematologic. The 42 patients with NSCLC had a response rate of 55%, a median survival of 10 months, and 41% were alive at one year after starting treatment. 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. 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. The cumulative risk at 12 years for these patients was 30%. Chest irradiation and continuing cigarette smoking contributed to the increased risk. A chemoprevention trial for this population has been organized.