ideasIdea
Model-informed individual dosing with drug-level monitoring for every oral cancer drug
People differ several-fold in how they absorb and clear cancer pills. Measure blood levels and adjust each person's dose, as is routine for some antibiotics and transplant drugs.
Exposure to oral kinase inhibitors and endocrine agents varies widely between patients and correlates with both toxicity and efficacy (imatinib, abiraterone, tamoxifen metabolites, sunitinib). Therapeutic drug monitoring is standard in other fields but rare in oncology. The proposal is a programme defining exposure targets for the top 30 oral anticancer drugs, a low-cost assay network, and model-informed precision dosing software integrated into prescribing, tested in randomised trials against fixed dosing.
Hypothesis
Exposure-guided dosing reduces grade 3+ toxicity and discontinuation by a third while maintaining or improving progression-free survival compared with fixed labelled dosing.
Rationale
Fixed dosing at the maximum tolerated dose ignores known pharmacokinetic variability; the analytic and modelling tools are mature and cheap relative to the drugs.
What would test it
Randomised trial of exposure-guided versus fixed dosing across five oral agents with composite toxicity-discontinuation primary and PFS non-inferiority secondary endpoints.
Maturity
early clinical
Who has to act
clinic
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.