ideasIdea
Upfront reduced-dose regimens tested head-to-head in frail older patients
Frail older patients are often given full doses and then have them cut after bad side effects, or are given nothing. Trials should test starting at a lower dose from the beginning.
The GO2 trial in frail patients with advanced gastro-oesophageal cancer showed that the lowest of three chemotherapy dose levels gave non-inferior progression-free survival with better patient experience. This design, comparing upfront dose levels rather than escalating after toxicity, is rarely used elsewhere. A programme of GO2-style trials across common cancers would give evidence for the many frail patients for whom current guidelines offer only extrapolation.
Hypothesis
In at least three common indications, an upfront reduced-dose regimen will be non-inferior for survival and superior for quality of life and treatment completion in frail older patients.
Rationale
GO2 provides a template; toxicity-driven dose reduction in practice means many patients already receive lower doses without evidence about which starting level is best.
What would test it
Fund three GO2-style randomised dose-level trials in frail older patients with lung, colorectal, and breast cancer, with overall treatment utility as a co-primary endpoint.
Maturity
early clinical
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
- 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.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.