Hennequin C, Favaudon V, Balosso J, Marty M, Maylin C
Service de cancérologie-radiothérapie, hôpital Saint-Louis, Paris.
Bull Cancer. 1994 Dec;81(12):1005-13.
Combination of radiotherapy and chemotherapy (CRC) is actually one important way of research in oncology. Theoretical advantages are: 1) Spatial cooperation; 2) Additivity, which is only obtained if the toxicity of each modality are different; 3) Supra-additivity, which needs a rigorous in vitro definition; the only way to prove it is to make an isobologram analysis. This model has however, some limitations: qualitative variable could not be used, results could be different, depending on the cell line and isoeffect chosen... In fact, a supra-additivity was only demonstrated for cisplatinum and etoposide. Interactions mechanisms were: 1) at the molecular level, creation of new lesions or inhibition of radiation lesions repair; 2) At the cellular level, either cytokinetic cooperation with S-phase dependent drugs, or synchronisation for the drugs which blocked the cells in M-phase; 3) At the tissular level, reoxygenation, cycle redistribution... In clinical practice, three mains schedules have been described: sequential, alternating and concomitant. Only the latter try to use the supra-additivity phenomena. Aims of CRC could be: improvement or in survival or in local control, preservation of an functional organ... Depending on the tumor site and aim of the CRC, some schedules had to be preferred. For head and neck cancers, alternating or concomitant schedules offer a better local control. In bronchial carcinomas, sequential administration of the two modalities reduce the metastatic rate, but not the local control. Concomitant schedule improve the local control rate only. In some conservative protocol of bladder cancers, sequential and concomitant administration were used. In conclusion, CRC begins to be the usual clinical practice. The present schedules could be improved with the help of laboratory findings, which are now more and more precise.
放化疗联合（CRC）实际上是肿瘤学研究的一种重要方式。理论优势有：1）空间协同作用；2）相加作用，只有当每种治疗方式的毒性不同时才能实现；3）超相加作用，这需要严格的体外定义；证明它的唯一方法是进行等效线图分析。然而，该模型存在一些局限性：不能使用定性变量，结果可能因细胞系和所选等效应不同而有所差异……事实上，仅顺铂和依托泊苷表现出超相加作用。相互作用机制包括：1）在分子水平，产生新的损伤或抑制放射损伤修复；2）在细胞水平，与S期依赖性药物进行细胞动力学协同作用，或使阻断细胞于M期的药物实现同步化；3）在组织水平，再氧合、周期重新分布……在临床实践中，已描述了三种主要方案：序贯、交替和同步。只有同步方案试图利用超相加作用现象。放化疗联合的目标可以是：提高生存率或局部控制率、保留功能器官……根据肿瘤部位和放化疗联合的目标，某些方案更受青睐。对于头颈癌，交替或同步方案能提供更好的局部控制。对于支气管癌，两种治疗方式序贯给药可降低转移率，但不能提高局部控制率。同步方案仅能提高局部控制率。在一些膀胱癌的保守治疗方案中，使用了序贯和同步给药。总之，放化疗联合开始成为常规临床实践。借助现在越来越精确的实验室研究结果，目前的方案可以得到改进。
