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

Source: https://onco.cc/ideas/idea-tr1-start-low-titrate-up-oral-agents/  
OnCo record `idea-tr1-start-low-titrate-up-oral-agents` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: industry

## Sources

- Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus

## Connected records

- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- drugs: [Abemaciclib](https://onco.cc/drugs/abemaciclib/), [Capivasertib](https://onco.cc/drugs/capivasertib/), [Niraparib](https://onco.cc/drugs/niraparib/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)

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