Gender and haemato-oncology: Aspects of pharmacokinetics and pharmacodynamics

Abstract

In the era of personalised medicine, it sounds surprising that gender aspects of tumour pharmacology have been seriously considered since the mid 1990s only. In parallel, cancer therapies have been the subject to several new treatment paradigms and novel therapeutic strategies which are all fuelled by the pipeline of new compounds necessary to realise tailored therapies. This plethora of novel options contrasts with the evidence about pharmacokinetic (PK) and pharmacodynamic (PD) differences in male and female subjects. To refine the term "difference" further, we should consider a distinction between gender disparities observed in experimental systems and the application to the clinical setting requiring a much higher level of evidence. Although there are convincing examples of PK (e.g. 5-fluorouracil) or PD differences (e.g. response in lung cancer treatment), gender disparities overlap with a variety of other confounding variables, most notably individual fitness, age, organ function, concurrent diseases, genetic/epigenetic background and others. Nowadays, gender per se is generally not a factor influencing dosing of anti-cancer drugs. Thus, the limited evidence on gender specific tumour pharmacology requires prospectively randomised clinical trials with gender oriented PK/PD endpoints in the form of PK/PD modelling to establish gender as a determinant in cancer pharmacology.