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Sex differences in the drug therapy for oncologic diseases

Item Type:Article
Title:Sex differences in the drug therapy for oncologic diseases
Creators Name:Schmetzer, O. and Floercken, A.
Abstract: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.
Keywords:Drug, Metabolism, Half-Life, Cytostatic Therapy, Gender
Source:Handbook of Experimental Pharmacology
Series Name:Handbook of Experimental Pharmacology
Title of Book:Sex differences in the drug therapy for oncologic diseases
Page Range:411-442
Official Publication:https://doi.org/10.1007/978-3-642-30726-3_19
PubMed:View item in PubMed

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