title: Sex differences in the drug therapy for oncologic diseases.
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.
authors.affiliation: Max-Delbrück-Centrum for Molecular Medicine Molecular Immunotherapy, Berlin, Germany. oliver.schmetzer@gmx.net
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmetzer
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012727:Sex Characteristics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases