{"entity":{"id":"idea-tr1-adaptive-therapy-randomised-phase-2","kind":"idea","name":"Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials","aka":[],"tldr":"Adaptive therapy uses just enough drug to keep a tumour in check, pausing when the burden falls and resuming when it rises, so drug-sensitive cells suppress resistant ones. A prostate cancer pilot with abiraterone lengthened time to progression against historical controls on half the drug; randomised phase 2 trials are the next step.","summary":"Adaptive therapy modulates dosing on tumour burden (PSA, imaging or ctDNA), pausing when burden falls below a threshold and resuming when it rises, to maintain a population of sensitive cells that compete with resistant clones. A pilot in metastatic castration-resistant prostate cancer using abiraterone showed prolonged time to progression versus historical controls with roughly half the cumulative drug. The proposal is randomised phase 2 trials in prostate, melanoma and ovarian cancer with pre-specified adaptive algorithms.","asOf":"2026-09-08","links":[{"label":"Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer (Nature Communications 2017)","url":"https://www.nature.com/articles/s41467-017-01968-5"}],"tags":[],"related":["prostate-roadmap","idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2"],"cancers":["prostate","melanoma","ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive dosing will extend time to progression by at least 30 percent relative to continuous dosing in at least one of three settings tested, with lower cumulative drug exposure.","rationale":"Evolutionary game theory and mathematical models of competition between sensitive and resistant clones predict that maximum-dose therapy selects fastest for resistance; the pilot data are consistent with the model.","test":"Three randomised phase 2 trials (n about 100 each) of adaptive versus continuous dosing with time to progression as the primary endpoint and cumulative dose and QoL as secondaries.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-adaptive-therapy-randomised-phase-2/","neighbours":{"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"idea":[{"id":"idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2","kind":"idea","name":"Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint","route":"/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/"}],"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"institution":[{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","kind":"paper","name":"TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer","route":"/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/"}]}}