# Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials

Source: https://onco.cc/ideas/idea-tr1-adaptive-therapy-randomised-phase-2/  
OnCo record `idea-tr1-adaptive-therapy-randomised-phase-2` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer (Nature Communications 2017): https://www.nature.com/articles/s41467-017-01968-5

## Connected records

- roadmaps: [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](https://onco.cc/roadmaps/prostate-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- ideas: [Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint](https://onco.cc/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/)
- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- institutions: [Moffitt Cancer Center](https://onco.cc/institutions/moffitt/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/)

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