Quantin X, Godard P, Michel F B, Pujol J L
Service des Maladies Respiratoires, CHU de Montpellier, Hôpital Arnaud de Villeneuve.
Rev Mal Respir. 1998 Oct;15(5):597-612.
This review presents a synthesis of published studies on the activity of the newer cytotoxic drugs in the treatment of bronchial cancer. It also touches on the early indications of recent results which until now have only been the subject of oral presentations. The taxanes form a new class of anti-cancer drug. Myelosuppression is their limiting factor. These are very active cytotoxic drugs but their toxological profile makes them difficult to use in polychemotherapy. The anti-tumour activity of docetaxel (Taxotere) has been shown. For non-small cell cancer (CNPC) the objective response (OR) is of the order of 26% in new patients and 21% in those who have been pre-treated with a combination of drugs based on Cisplatine. For paclitaxel (Taxol) the OR is around 25% in new patients. In association with a course of cisplatine the efficacy would be dose dependent. For small cell cancer (CPC) it enables a level of OR around 38% as monochemotherapy. Inhibitors of topoisomerase I (topotecan, irinotecan) form another new class of therapy. Myelosuppression again limits their toxicity. Diarrhoea is an additional toxicity of irinotecan (Campto). The inhibitors of topoisomerase I seem particularly active as monochemotherapy in the treatment of smal cell cancer. Haematological toxicity makes them difficult in association. The activity of topotecan (Hycantin) in the treatment of non-small cell carcinoma remains to be studied. For this indication irinotecan would enable an OR of 33% in new patients. The new anti-metabolite, gemcitabine (Gemzar) is characterised by a different mode of action from other cytotoxics used in the treatment of bronchial cancer. For non-small cell carcinoma it is active as monotherapy and in association with cisplatine. Its activity is more modest in the treatment of CPC but few studies are available for this indication. Its toxic profile makes it promising to be used in association. The new spindle drug vinorelbine (Navelbine) is active as monotherapy or associated with cisplatine in the treatment of non-small cell carcinoma. The limiting toxicity is haematological. Its neurotoxicity is moderate compared to agents in the same therapeutic class. These different cytotoxic drugs arouse a ligitimate interest but the optimal therapeutic schemas for their use remain poorly understood (with the exception of vinorelbine). Their place in the therapeutic arsenal remains to be defined whilst waiting for the results of Phase III studies, their routine use cannot be recommended.
本综述对已发表的关于新型细胞毒性药物治疗支气管癌活性的研究进行了综合分析。它还探讨了近期结果的早期迹象，这些结果迄今为止仅在口头报告中提及。紫杉烷类形成了一类新的抗癌药物。骨髓抑制是其限制因素。这些是非常有效的细胞毒性药物，但它们的毒理学特征使其难以用于联合化疗。多西他赛（泰索帝）的抗肿瘤活性已得到证实。对于非小细胞癌（NSCLC），新患者的客观缓解率（OR）约为26%，接受过基于顺铂的联合药物预处理的患者为21%。对于紫杉醇（泰素），新患者的OR约为25%。与顺铂疗程联合使用时，疗效将取决于剂量。对于小细胞癌（SCLC），作为单一化疗药物，其OR水平约为38%。拓扑异构酶I抑制剂（拓扑替康、伊立替康）构成了另一类新的治疗药物。骨髓抑制再次限制了它们的毒性。腹泻是伊立替康（开普拓）的另一种毒性。拓扑异构酶I抑制剂在治疗小细胞癌方面作为单一化疗药物似乎特别有效。血液学毒性使其难以联合使用。拓扑替康（海特琴）在治疗非小细胞癌方面的活性仍有待研究。对于该适应症，伊立替康在新患者中的OR为33%。新型抗代谢药物吉西他滨（健择）的作用方式与用于治疗支气管癌的其他细胞毒性药物不同。对于非小细胞癌，它作为单一疗法以及与顺铂联合使用时均有活性。其在治疗SCLC方面的活性较低，但针对该适应症的研究较少。其毒性特征使其有望用于联合治疗。新型纺锤体药物长春瑞滨（诺维本）在治疗非小细胞癌时作为单一疗法或与顺铂联合使用均有活性。限制毒性为血液学毒性。与同一治疗类别的药物相比，其神经毒性较轻。这些不同的细胞毒性药物引起了合理的关注，但除长春瑞滨外，它们的最佳治疗方案仍知之甚少。在等待III期研究结果的同时，它们在治疗武器库中的地位仍有待确定，目前不建议常规使用。
