Freyer G, Maire P, Ardiet C, Tranchand B, Droz J P
Départment de médecine carcinologique, centre Léon-Bérard, Lyon, France.
Bull Cancer. 1995 Jul;82(7):531-40.
Cancer in elderly people accounts for more than 50% of the malignant tumors treated per year in France and this population of patients has a rather high-life expectancy. Chemotherapy is active in these elderly patients but clearly more toxic than for young ones. The general tendency among the physicians to empirically reduce the doses is due to the known increased risk of unexpected toxicities. That is why there is such a large variety of conflicting opinions in the literature concerning the benefit and toxic effects of cytostatic drugs in the elderly. Therefore, it appears consistent to adjust chemotherapy regimen according to physiological criteria. Among them is biological age which is a better parameter than chronological age to describe the biological heterogeneity of this population of patients. Nakamura et al have published an interesting model for the calculation of biological age by principal component analysis using 11 easily measurable biological and clinical variables in a series of healthy elderly people. This kind of approach is not at present available for cancer patients but it allows to demonstrate that the chronological age is only one among many other age-related variables and is not sufficient to fully describe it. The variations in pharmacokinetic data are more frequent in the elderly than in younger people and this reflects age-related physiological heterogeneity. This factor is well taken into account in recently described population pharmacokinetic models, bayesian fittings and adaptative control which may represent promising approaches of cytostatics dose adjustments. Such models have been successfully developed in young patients receiving doxorubicin, methotrexate, melphalan and teniposide. They require a low number of blood samples to determine individual parameters and further adjust the doses, and are therefore of potential interest in old patients. Prospective studies are warranted in the future in order to recommend their use in the elderly.
在法国，老年癌症患者占每年接受治疗的恶性肿瘤患者的50%以上，而且这群患者的预期寿命相当高。化疗对这些老年患者有效，但明显比年轻患者毒性更大。医生们普遍倾向于凭经验减少剂量，这是因为已知意外毒性风险增加。这就是为什么文献中关于细胞毒性药物在老年人中的益处和毒性作用存在如此多相互矛盾的观点。因此，根据生理标准调整化疗方案似乎是合理的。其中生物年龄是比实际年龄更好的参数，能用来描述这群患者的生物异质性。中村等人发表了一个有趣的模型，通过主成分分析，利用一系列健康老年人的11个易于测量的生物和临床变量来计算生物年龄。目前这种方法不适用于癌症患者，但它能证明实际年龄只是众多与年龄相关的变量之一，不足以全面描述它。老年人药代动力学数据的变化比年轻人更频繁，这反映了与年龄相关的生理异质性。最近描述的群体药代动力学模型、贝叶斯拟合和自适应控制充分考虑了这一因素，这些可能代表了细胞毒性药物剂量调整的有前景的方法。这样的模型已在接受阿霉素、甲氨蝶呤、美法仑和替尼泊苷治疗的年轻患者中成功开发。它们只需少量血样就能确定个体参数并进一步调整剂量，因此对老年患者可能有潜在价值。未来有必要进行前瞻性研究，以便推荐在老年人中使用这些方法。
