Adaptive therapy (evolution-based dosing)
Instead of hitting a tumour as hard as possible, adaptive therapy gives just enough drug to keep it in check and stops when it shrinks, so drug-sensitive cells survive to compete with resistant ones. A pilot trial in prostate cancer roughly doubled the time to progression on abiraterone.
Overview
Robert Gatenby and colleagues at Moffitt proposed in 2009 that maximum-tolerated-dose therapy selects for resistance by eliminating the sensitive cells that would otherwise suppress resistant ones through competition. Adaptive therapy uses tumour burden (PSA, imaging) to modulate dosing: treat until the marker halves, pause, resume when it returns. Zhang and colleagues' pilot trial (2017) in metastatic castration-resistant prostate cancer gave abiraterone adaptively and reported a median time to progression of about 30 months against roughly 14 in contemporaneous continuous-dosing patients, using about half the drug. Randomised trials in prostate cancer (ANZadapt), melanoma and other tumours are under way, and the approach depends on mathematical models of competition to set thresholds.
How it works
Lotka-Volterra competition between sensitive and resistant clones: keeping a sensitive population alive imposes a fitness cost on resistant cells, delaying their takeover; dosing is adjusted to hold the tumour at a stable burden.
- Doubled time to progression in the pilot trial with half the drug
- Uses existing drugs and markers
- Grounded in evolutionary theory
- Randomised evidence still pending
- Requires a reliable, frequent burden marker
- Threshold choice is model dependent
Latest papers
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