{"entity":{"id":"idea-tr1-response-adapted-dose-reduction","kind":"idea","name":"Reduce the dose once the cancer responds: response-adapted de-escalation trials","aka":[],"tldr":"The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.","summary":"Randomised trials in which patients achieving a defined response (radiographic, molecular or biochemical) after induction are allocated to continue full dose or step down to a maintenance dose (e.g., 50 percent), with resumption of full dose on progression. Precedents include dose reduction of dasatinib and other TKIs in chronic-phase CML after deep response, and maintenance de-escalation strategies in myeloma; the proposal extends the approach to solid-tumour targeted agents and ADCs where chronic toxicity accumulates.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["cll","multiple-myeloma","breast-her2-positive"],"sections":[],"technologies":["kinase-inhibitors","adc"],"targets":[],"drugs":["imatinib","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Response-adapted de-escalation will be non-inferior for PFS with a substantial reduction in cumulative toxicity and cost, and progression on the reduced dose will be salvageable by re-escalation in most cases.","rationale":"Tumour burden and the number of cells that must be suppressed fall after response; pharmacological suppression of residual disease may require less exposure than debulking, as CML dose-reduction studies suggest.","test":"Randomised phase 3 non-inferiority trials in two settings (an oral targeted agent in a solid tumour and an ADC) with PFS primary and cumulative toxicity, QoL and cost as secondaries.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-response-adapted-dose-reduction/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}