ideasIdea
Dose-finding in older and frail patients, not extrapolation from fit ones
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.
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.
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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Older and multimorbid patients are excluded and undertreated · Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority.