# Rotate between drugs on a fixed schedule instead of waiting for failure

Source: https://onco.cc/ideas/idea-bio1-alternating-schedules/  
OnCo record `idea-bio1-alternating-schedules` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Hospitals rotate antibiotics to stop bacteria adapting. Cycling between two cancer drugs on a set schedule, rather than using one until it fails, might work the same way.

## Summary

Antibiotic cycling and mixing are used to manage resistance in intensive care, with mathematical models predicting when each is superior. In oncology, drugs are almost always given until failure. Where two agents with non-overlapping resistance mechanisms and tolerable toxicity exist, scheduled rotation before resistance is established could keep both populations suppressed. Modelling should precede the trial to choose cycle length.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Scheduled rotation between two non-cross-resistant agents extends time to progression compared with sequential use of the same agents, with equivalent cumulative toxicity.
- Rationale: Rotation denies any single clone a sustained selective advantage; the approach requires only existing drugs and a schedule change, making it unusually cheap to test.
- Proposed test: Model-informed randomised phase 2 in a setting with two well-tolerated non-cross-resistant options (for example endocrine agents or maintenance regimens), comparing rotation with sequence.
- Maturity: speculative
- Actor: research

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- ideas: [Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer](https://onco.cc/ideas/idea-prostate-randomise-the-sequence-not-only-the-drugs/), [Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint](https://onco.cc/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/)
- terms: [Bipolar androgen therapy (BAT)](https://onco.cc/terms/bipolar-androgen-therapy/), [Intermittent androgen deprivation (IAD)](https://onco.cc/terms/intermittent-androgen-deprivation/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/)
- key papers: [RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018/)

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