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Sex differences in cancer chemotherapy effects, and why we need to reconsider BSA-based dosing of chemotherapy
  1. Anna Dorothea Wagner
  1. Department of oncology, Division of medical oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
  1. Correspondence to Dr. Anna Dorothea Wagner; Dorothea.Wagner{at}chuv.ch

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One sees only what one knows.

Johann Wolfgang von Goethe

Thus we ignore what we don’t know.

In oncology, it is traditionally assumed that men and women are equal. As a result, sex differences in treatment effects and the biology of non-sex-related cancers have largely been ignored in the last decades. However, the observation of increased chemotherapy toxicity in women is not new. Although overall insufficiently studied, available data from different types of tumours1–4 clearly demonstrate that women are more susceptible to toxicity from various types of chemotherapy.

Why do differences in toxicity exist?

Theoretically, sex differences in drug effects can be broken down into two categories:

  1. Differences in pharmacokinetics: sex differences in pharmacokinetics have been reviewed elsewhere5 and affect the different types of pharmacokinetic parameters, such as bioavailability, distribution, metabolism and excretion.6 Examples for chemotherapeutic drugs with significant sex differences in pharmacokinetics are 5-fluouracil7 and paclitaxel.8 However, the impact of the patients’ sex is most often not analysed, and/or subgroup analyses according to sex are not reported in pharmacokinetic studies and clinical trials. According to a recent literature survey of population pharmacokinetic studies of anticancer drugs,9 among 256 studies identified, only 80 reported sex as a tested covariate.

  2. Differences in pharmacodynamics: in addition to differences in drug metabolism, the sensitivity of both normal tissues and tumours in men and women may be different. Furthermore, the dose–response and dose-toxicity relationships may not necessarily be the same in both sexes.

Sex differences in treatment effects go beyond differences in toxicity

While differences in incidence and mortality of different types of cancers have initially been attributed to differences in exposure to risk factors, evidence from large epidemiologic studies clearly indicates significant sex differences in susceptibility and survival of non-sex-related cancers, which cannot be explained by differences in behaviour. Clocchiatti and colleagues introduced the term ‘sexual dimorphism …

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