Eberhardt W
Inneren Klinik und Poliklinik (Tumorforschung), Westdeutschen Tumorzentrum Essen.
Praxis (Bern 1994). 1997 Oct 15;86(42):1647-53.
Induction chemotherapies followed by concurrent chemoradiotherapy and definitive surgery have been tested in Essen since 1991 in a large phase-II study for patients with locally (far) advanced non-small cell lung cancer (NSCLC) stages IIIA (N2) and IIIB (T4, N3). After a median follow-up time of 43 months, mature long-term survival data for this intensive multimodality treatment program can now be reported. With nearly 1/3 of these patients experiencing long-term survival at 4 and 5 years after this approach, a significant improvement of long-term prognosis seems to have been achieved, because retrospective comparisons have demonstrated a rather unfavourable prognosis for these disease stages. However, new standards in the treatment for these disease stages could only be defined in the setting of national or international phase-III trials. Based on these promising results, a prospective randomized phase-III study has been planned for patients with stage IIIA (N2) as well as for centrally far advanced T3-tumors and one year ago patient accrual for this study has been started oligoinstitutionally. The standard arm of this study consists of upfront surgery followed by adjuvant radiation therapy, whereas for the experimental arm our Essen protocol a combination of induction chemotherapy with concurrent chemoradiation followed by surgery has been chosen. Meanwhile this prospective randomized trial has gained national support by the "Deutsche Krebshilfe". For stage IIIB (excluding patients with malignant pleural effusion or supraclavicular nodes) a further prospective randomized trial is on its way testing chemotherapy followed by a definitive concurrent chemoradiation approach up to 65 Gy radiation dose versus a multimodality program similar to our phase-II protocol with the inclusion of definitive surgery. Smaller phase-I and -II trials will search for alternative possibilities to improve the induction protocol first of all by the inclusion of new active drugs and secondly by increasing the chemotherapeutic dose intensity of the substances used so far. Due to the promising long-term results of the multimodality treatment programs published so far, these unfavourable patients with locally advanced NSCLC have now gained particular interest due to the development of now curatively intended treatment approaches.
自1991年起,在埃森针对局部(远处)晚期非小细胞肺癌(NSCLC)IIIA期(N2)和IIIB期(T4,N3)患者开展了一项大型II期研究,对诱导化疗后序贯同步放化疗及根治性手术进行了测试。经过43个月的中位随访时间,现在可以报告这一强化多模式治疗方案的成熟长期生存数据。采用这种方法后,近1/3的患者在4年和5年时实现长期生存,长期预后似乎有了显著改善,因为回顾性比较显示这些疾病阶段的预后相当不利。然而,只有在国家或国际III期试验的背景下才能确定这些疾病阶段的治疗新标准。基于这些令人鼓舞的结果,已计划针对IIIA期(N2)患者以及中心性远处晚期T3肿瘤患者开展一项前瞻性随机III期研究,一年前已在少数机构开始该研究的患者入组工作。该研究的标准组为先行手术,然后进行辅助放疗;而试验组则采用我们埃森方案,即诱导化疗联合同步放化疗后再行手术。与此同时,这项前瞻性随机试验已获得“德国癌症援助会”的全国支持。对于IIIB期(不包括有恶性胸腔积液或锁骨上淋巴结转移的患者),另一项前瞻性随机试验正在进行,比较化疗后序贯高达65 Gy放疗剂量的确定性同步放化疗方法与类似于我们II期方案并包括根治性手术的多模式方案。规模较小的I期和II期试验将首先通过纳入新的活性药物以及其次通过提高目前所用药物的化疗剂量强度来寻找改进诱导方案的替代可能性。由于目前已发表多模式治疗方案的长期结果令人鼓舞,这些局部晚期NSCLC的难治性患者因目前旨在治愈的治疗方法发展而受到特别关注