ideasIdea
Analyse and dose by sex: women get more toxicity from many cancer drugs at the same dose
Women experience more severe side effects from many chemotherapy, targeted and immune drugs than men at identical doses. Trials should analyse drug levels and side effects separately by sex and test whether women need different doses.
Registrational trials pre-specify sex-stratified PK, exposure-response and toxicity analyses; where exposure or toxicity differs, dose-finding includes sex-specific cohorts and labels carry sex-specific guidance. Fluorouracil, several TKIs and immune checkpoint inhibitors show sex differences in toxicity in pooled analyses; the mechanism (body composition, clearance, immune biology) varies by drug.
Hypothesis
Sex-stratified analysis will reveal clinically relevant exposure differences for a meaningful fraction of agents, and sex-adjusted dosing will reduce grade 3+ toxicity in women without reducing efficacy.
Rationale
Sex is the most basic stratifier and is routinely ignored in dose selection; pharmacology differences by sex are documented and body-surface-area dosing does not remove them.
What would test it
Pooled re-analysis of existing trial datasets by sex for toxicity and exposure; then a randomised sex-adjusted dosing study of one agent with a documented difference.
Maturity
early clinical
Who has to act
industry
Cost to try
Small (under $1M)
Years to first evidence
3
Bottlenecks it attacks
- Trials do not represent the people who get cancer · Older, Black, Hispanic, Asian, rural, poor and multimorbid patients are under-represented, so results may not apply to them.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.