# Dose-finding in older and frail patients, not extrapolation from fit ones

Source: https://onco.cc/ideas/idea-tr1-geriatric-dose-finding-cohorts/  
OnCo record `idea-tr1-geriatric-dose-finding-cohorts` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Geriatric assessment](https://onco.cc/technologies/geriatric-assessment/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [GAP70+: a geriatric assessment before chemotherapy cut serious toxicity in older adults by a fifth](https://onco.cc/key-papers/paper-gap70-geriatric-assessment-lancet-2021/)

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