# Analyse and dose by sex: women get more toxicity from many cancer drugs at the same dose

Source: https://onco.cc/ideas/idea-tr1-sex-stratified-pk-and-dosing/  
OnCo record `idea-tr1-sex-stratified-pk-and-dosing` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Women get more severe side effects than men at identical doses of fluorouracil, several kinase inhibitors and immune checkpoint inhibitors in pooled analyses. Trials should pre-specify sex-stratified drug level and toxicity analyses and, where they differ, run sex-specific dose-finding and label accordingly.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: industry

## Sources

- Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019): https://doi.org/10.1001/jamaoncol.2019.1870

## Connected records

- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Trials do not represent the people who get cancer](https://onco.cc/bottlenecks/b-trial-diversity/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018](https://onco.cc/key-papers/paper-loree-jama-oncol/)

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