Schmetzer Oliver, Flörcken Anne
Max-Delbrück-Centrum for Molecular Medicine Molecular Immunotherapy, Berlin, Germany.
Handb Exp Pharmacol. 2012(214):411-42. doi: 10.1007/978-3-642-30726-3_19.
There are clear gender-dependent differences in response rates and the probability of side effects in patients treated with chemotherapy. Sex-biased expression levels of metabolic enzymes and transporters in liver and kidney leading to different pharmacokinetics have been described for most common anti-cancer drugs. In women, half-life is often longer, which is associated with improved survival, but also increased toxicity.Some chemotherapy protocols lead to a better response rate in women without increasing toxicity (e.g., cisplatin and irinotecan), while others only increase toxicity, but do not improve response rates in women (e.g., 5-fluorouracil). The increased toxicity often correlates with different pharmacokinetics, but women also show a higher sensitivity to some agents with shorter half-life (e.g., steroids). Organ-specific toxicities like cardiac toxicity after doxorubicin treatment or neurotoxicity associated with ifosfamide are more severe in women due to gender-specific changes in gene expression. Novel therapies like tyrosine kinase inhibitors or monoclonal antibodies show very complex, but clinical significant differences depending on gender. Antibodies often have a longer half-life in women, which is associated with an improved response to therapy.Side effects appear to be highly dependent on different tissue properties, as women have a higher incidence of oral mucositis, but lower rates of gut toxicity. Nausea and vomiting is a greater problem in females during therapy due to the lower activity of anti-emetic drugs. Nausea and vomiting pose a bigger challenge in female patients, as anti-emetic drugs seem to be less effective.
接受化疗的患者在反应率和出现副作用的概率方面存在明显的性别差异。对于大多数常见抗癌药物，肝脏和肾脏中代谢酶和转运蛋白的性别偏向性表达水平会导致不同的药代动力学。在女性中，半衰期通常更长，这与生存率提高相关，但也会增加毒性。一些化疗方案在不增加毒性的情况下使女性有更好的反应率（如顺铂和伊立替康），而另一些方案仅增加毒性，但并未提高女性的反应率（如5-氟尿嘧啶）。毒性增加通常与不同的药代动力学相关，但女性对一些半衰期较短的药物（如类固醇）也表现出更高的敏感性。多柔比星治疗后的心脏毒性或与异环磷酰胺相关的神经毒性等器官特异性毒性在女性中由于基因表达的性别特异性变化而更为严重。酪氨酸激酶抑制剂或单克隆抗体等新型疗法表现出非常复杂但取决于性别的临床显著差异。抗体在女性体内的半衰期通常更长，这与对治疗的反应改善相关。副作用似乎高度依赖于不同的组织特性，因为女性口腔黏膜炎的发生率较高，但肠道毒性发生率较低。在治疗期间，恶心和呕吐在女性中是一个更大的问题，因为止吐药物的活性较低。恶心和呕吐对女性患者构成了更大的挑战，因为止吐药物似乎效果较差。
