OnCo
ideasIdea

Start low and step up: individualised titration of oral cancer drugs, randomised

Instead of starting everyone on the full dose and cutting back after side effects, start lower and increase in patients who tolerate it. This keeps more people on treatment and is how blood-pressure drugs are given.

Randomised comparisons of standard full-dose start versus a step-up schedule (starting at 50-70 percent of label dose, escalating at cycle 2-3 in the absence of toxicity) for oral agents with high early discontinuation rates (some PARP inhibitors, multi-kinase inhibitors, CDK4/6 inhibitors, PI3K/AKT inhibitors). Niraparib's individualised starting dose by weight and platelet count is a precedent that improved tolerability without loss of efficacy.

Hypothesis
Step-up dosing will reduce early discontinuation and grade 3+ toxicity in the first three cycles by at least a third, with non-inferior PFS, for agents with exposure-driven early toxicity.
Rationale
Early toxicity drives discontinuation before benefit can accrue; many patients who reduce dose after toxicity do as well as those who do not, suggesting the starting dose is too high for a subset.
What would test it
Randomised phase 3 non-inferiority trials of step-up versus full-dose starts for two oral agents with documented high early discontinuation, powered for PFS with discontinuation as key secondary.
Maturity
early clinical
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks

Connected

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Pages like this

not linked directly; found by shared links

technologies

2
CDK4/6 inhibitorsPARP inhibitors

drugs

3
ApprovedSmall-molecule CDK4/6 inhibitor
Abemaciclib · Verzenio
ApprovedSmall-molecule AKT inhibitor
Capivasertib · Truqap
ApprovedSmall-molecule PARP inhibitor
Niraparib · Zejula

bottlenecks

2
Toxicity and quality of life are undervaluedWrong doses