{"entity":{"id":"idea-tr1-geriatric-dose-finding-cohorts","kind":"idea","name":"Dose-finding in older and frail patients, not extrapolation from fit ones","aka":[],"tldr":"The dose for a frail 80-year-old is guessed from what fit 55-year-olds tolerated. Running dose-finding in older patients directly, using frailty assessment, would give doses they can actually take.","summary":"Dedicated dose-finding and dose-comparison cohorts in patients aged 75 and over or with frailty on geriatric assessment, run in parallel with or after the main dose-finding, using tolerability, function and QoL alongside efficacy. The GO2 trial in advanced oesophago-gastric cancer showed that reduced-intensity chemotherapy in frail and older patients was non-inferior with better QoL, demonstrating the approach.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["gastric","esophageal","aml"],"sections":[],"technologies":["geriatric-assessment","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Frailty-stratified dose finding will define lower recommended doses for frail patients for most agents studied, with non-inferior disease control and better patient-reported outcomes than label dosing.","rationale":"Pharmacokinetics, organ reserve and tolerance differ with age and frailty; real-world discontinuation in older patients is high, and a 'start full dose and reduce' approach loses patients early.","test":"Embed a frailty-stratified dose cohort in three new-agent programmes and one randomised reduced-dose trial in a frail population per year, tracking label statements and outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr1-geriatric-dose-finding-cohorts/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"geriatric-assessment","kind":"technology","name":"Geriatric assessment","route":"/technologies/geriatric-assessment/"}],"bottleneck":[{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-gap70-geriatric-assessment-lancet-2021","kind":"paper","name":"GAP70+: a geriatric assessment before chemotherapy cut serious toxicity in older adults by a fifth","route":"/key-papers/paper-gap70-geriatric-assessment-lancet-2021/"}]}}