{"entity":{"id":"idea-acc-upfront-reduced-dose-trials-frail","kind":"idea","name":"Upfront reduced-dose regimens tested head-to-head in frail older patients","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"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)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":["gastric","esophageal","colorectal"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-dose-optimisation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":4},"route":"/ideas/idea-acc-upfront-reduced-dose-trials-frail/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"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/"}],"bottleneck":[{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"},{"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/"}]}}