Steward W P, Dunlop D J
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Ann Oncol. 1995;6 Suppl 1:49-54. doi: 10.1093/annonc/6.suppl_1.s49.
Non-small cell lung cancer accounts for 75% of all lung tumours, and only about 10% of patients will remain alive 5 years after diagnosis. Few cytotoxic drugs currently registered produce more than a 15% response rate as a single agent or 30%-35% in combination, with only modest survival benefits. New cytotoxic drugs entering phase II and III studies, however, appear to have more than 20% activity against this disease. They include the taxanes (taxol and taxotere), camptothecin analogues (CPT-11 and topotecan), antimetabolites (edatrexate and gemcitabine) and the vinca alkaloid, navelbine. Taxol produces response rates of about 25% in previously untreated patients and is currently undergoing trials at higher doses in combination with cisplatin and granulocyte colony-stimulating factor. Taxotere produces response rates of 33% in previously untreated patients and 21% in patients previously refractory to platinum-containing regimens. The camptothecin analogues, which are inhibitors of topoisomerase I, may produce response rates of up to 41% in previously untreated patients, but these results have varied considerably between different trials (response rates as low as 13.5% have been reported for topotecan). A phase II study with edatrexate produced a response rate of 32% but subsequent trials using combination chemotherapy including this agent have been disappointing. The activity of gemcitabine as a single agent is 20%-25%. Three ongoing phase II studies combining cisplatin and gemcitabine have shown response rates of up to 50%. Gemcitabine has minimal subjective toxicity. Navelbine produces response rates of 22%-33% as a single agent and up to 65% in combination. These new cytotoxic agents with significant activity in non-small cell lung cancer provide exciting potential for developing novel combination regimens in the advanced setting and as neoadjuvant and adjuvant therapy.
非小细胞肺癌占所有肺部肿瘤的75%，确诊后只有约10%的患者能存活5年。目前注册的细胞毒性药物作为单一药物使用时，有效率超过15%，联合使用时有效率为30%-35%，生存获益有限。然而，进入II期和III期研究的新型细胞毒性药物对该疾病的活性似乎超过20%。它们包括紫杉烷类（紫杉醇和多西他赛）、喜树碱类似物（伊立替康和拓扑替康）、抗代谢物（依达曲沙和吉西他滨）以及长春花生物碱长春瑞滨。紫杉醇在未经治疗的患者中有效率约为25%，目前正在进行更高剂量与顺铂和粒细胞集落刺激因子联合使用的试验。多西他赛在未经治疗的患者中有效率为33%，在先前对含铂方案耐药的患者中有效率为21%。喜树碱类似物是拓扑异构酶I的抑制剂，在未经治疗的患者中有效率可能高达41%，但不同试验的结果差异很大（拓扑替康的有效率低至13.5%）。依达曲沙的II期研究有效率为32%，但随后使用含该药物的联合化疗试验令人失望。吉西他滨作为单一药物的活性为20%-25%。三项正在进行的顺铂和吉西他滨联合II期研究显示有效率高达50%。吉西他滨的主观毒性极小。长春瑞滨作为单一药物的有效率为22%-33%，联合使用时高达65%。这些在非小细胞肺癌中具有显著活性的新型细胞毒性药物为在晚期情况下以及作为新辅助和辅助治疗开发新型联合方案提供了令人兴奋的潜力。
