{"entity":{"id":"idea-tr1-sex-stratified-pk-and-dosing","kind":"idea","name":"Analyse and dose by sex: women get more toxicity from many cancer drugs at the same dose","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"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)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-dose-optimisation","b-toxicity-qol"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"small","horizonYears":3},"route":"/ideas/idea-tr1-sex-stratified-pk-and-dosing/","neighbours":{"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-loree-jama-oncol","kind":"paper","name":"Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018","route":"/key-papers/paper-loree-jama-oncol/"}]}}