ideasIdea
Measure blood levels of oral targeted drugs and adjust doses to a target range
Blood levels of oral cancer pills vary several-fold between people on the same dose, so some are under-treated and others poisoned. Checking levels and adjusting the dose, as is routine for some antibiotics, could fix both.
Therapeutic drug monitoring (TDM) for oral kinase inhibitors and hormonal agents with established exposure-response relationships and high inter-patient variability (imatinib, sunitinib, pazopanib, abiraterone, tamoxifen via endoxifen, and newer agents), with dose adjustment to a target trough. Dutch multicentre TDM studies have shown feasibility and increased target attainment; outcome-powered randomised trials are lacking.
Hypothesis
TDM-guided dosing will increase the proportion of patients within the target exposure range from roughly half to over 80 percent and will improve PFS or reduce grade 3+ toxicity relative to fixed dosing in a randomised comparison.
Rationale
Adherence, food, interactions and pharmacogenetics cause large exposure variability; fixed dosing ignores it. TDM is standard for narrow-therapeutic-index drugs in other fields.
What would test it
A randomised trial of TDM-guided versus fixed dosing for two or three TKIs with the strongest exposure-response evidence, with PFS and toxicity endpoints.
Maturity
early clinical
Who has to act
clinic
Cost to try
Small (under $1M)
Years to first evidence
3
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.