Tannock I F
Department of Medicine, Princess Margaret Hospital, Toronto, Ontario, Canada.
Lung Cancer. 1994 Mar;10 Suppl 1:S29-51. doi: 10.1016/0169-5002(94)91665-9.
Strategies for developing combined modality treatment for lung cancer have, until now, depended largely on empirical approaches whereby drugs with some activity against advanced disease have been combined with radiation. Survival gains have been modest. The present article emphasizes the need for new approaches that are based on mechanisms of interaction or cooperation between radiation and drugs, such that there is a selective increase in killing of tumour cells. Potential interactions include the use of radiation and drugs to eliminate cell populations which are shown in predictive assays to have differing mechanisms of resistance to the two modalities, selective inhibition of repopulation of tumour cells during radiotherapy by using drugs or biological agents, and selective killing of cells in hypoxic or acidic regions of tumours. The feasibility and potential of such approaches should be evaluated initially in small single-arm studies where outcome in individual patients is related to biological studies of mechanism. Such treatment may need to be individualized (e.g. depending on markers of drug resistance or growth factor receptors). Ultimately, the value of such treatments will need to be evaluated (whether individualized or generic) against standard treatment in large randomized trials. Guidelines for the conduct of such trials are indicated with emphasis on quality of life, assessment of costs and benefits, and involvement of patients in clinical decision making.
迄今为止，肺癌联合治疗方案的制定很大程度上依赖于经验方法，即把对晚期疾病有一定活性的药物与放疗相结合。生存率的提高幅度不大。本文强调需要基于放疗与药物之间相互作用或协同机制的新方法，以便选择性地增加肿瘤细胞的杀伤。潜在的相互作用包括利用放疗和药物消除在预测性检测中显示对这两种治疗方式有不同耐药机制的细胞群体，通过使用药物或生物制剂在放疗期间选择性抑制肿瘤细胞的再增殖，以及选择性杀伤肿瘤低氧或酸性区域的细胞。此类方法的可行性和潜力应首先在小型单臂研究中进行评估，其中个体患者的预后与机制的生物学研究相关。此类治疗可能需要个体化（例如，取决于耐药标志物或生长因子受体）。最终，此类治疗的价值（无论是个体化还是通用的）需要在大型随机试验中与标准治疗进行对比评估。文中指出了开展此类试验的指导原则，重点强调生活质量、成本效益评估以及患者参与临床决策。
