Einhorn L H
Department of Medicine, Indiana University Medical Center, Indianapolis 46202, USA.
Semin Oncol. 1997 Jun;24(3 Suppl 8):S8-24-S8-26.
Although non-small cell lung cancer accounts for a majority of lung cancer cases in the United States, overall response rates of only 20% have been obtained with cisplatin-based therapy. However, new agents such as the nucleoside analog gemcitabine have demonstrated single-agent response rates of approximately 20%. The synergistic growth inhibition of several tumor cell lines seen in vitro with cisplatin and gemcitabine has led to clinical trials incorporating this drug combination. Recent phase I trials revealed that administration of gemcitabine 1,000 mg/m2 weekly x 3, with cisplatin 100 mg/m2 on day 15, every 28 days, was well tolerated. This regimen was used in the present Hoosier Oncology Group phase II trial of patients with advanced non-small cell lung cancer, except that cisplatin was administered on day 1. Five patients had stage IIIB and 25 had stage IV disease, with a mean Karnofsky performance status of 90. Toxicity observed was primarily hematologic, notably, granulocytopenia and thrombocytopenia. Responses were seen in 10 of 27 patients, for an overall response rate of 37%. Median overall survival was 8.4 months; it was 10.2 months for patients with stage IV disease. These favorable results and manageable side effects suggest that future trials incorporating gemcitabine and cisplatin are indicated.
在美国，虽然非小细胞肺癌占肺癌病例的大多数，但基于顺铂的治疗总体缓解率仅为20%。然而，新的药物如核苷类似物吉西他滨已显示单药缓解率约为20%。体外观察到顺铂和吉西他滨对几种肿瘤细胞系具有协同生长抑制作用，这促使开展了包含这种药物组合的临床试验。最近的I期试验表明，每28天，在第15天给予顺铂100mg/m²，每周给予吉西他滨1000mg/m²，共3周，耐受性良好。本印第安纳肿瘤学组II期晚期非小细胞肺癌患者试验采用了该方案，只是顺铂在第1天给药。5例患者为IIIB期，25例为IV期，卡诺夫斯基功能状态平均为90。观察到的毒性主要是血液学毒性，尤其是粒细胞减少和血小板减少。27例患者中有10例出现缓解，总体缓解率为37%。中位总生存期为8.4个月；IV期患者为10.2个月。这些良好的结果和可控制的副作用表明，未来应开展包含吉西他滨和顺铂的试验。
