# Upfront reduced-dose regimens tested head-to-head in frail older patients

Source: https://onco.cc/ideas/idea-acc-upfront-reduced-dose-trials-frail/  
OnCo record `idea-acc-upfront-reduced-dose-trials-frail` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: research

## Sources

- Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021): https://doi.org/10.1016/S0140-6736(21)01789-X

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [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/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/), [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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