OnCo
ideasIdea

Reduce the dose once the cancer responds: response-adapted de-escalation trials

The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.

Randomised trials in which patients achieving a defined response (radiographic, molecular or biochemical) after induction are allocated to continue full dose or step down to a maintenance dose (e.g., 50 percent), with resumption of full dose on progression. Precedents include dose reduction of dasatinib and other TKIs in chronic-phase CML after deep response, and maintenance de-escalation strategies in myeloma; the proposal extends the approach to solid-tumour targeted agents and ADCs where chronic toxicity accumulates.

Hypothesis
Response-adapted de-escalation will be non-inferior for PFS with a substantial reduction in cumulative toxicity and cost, and progression on the reduced dose will be salvageable by re-escalation in most cases.
Rationale
Tumour burden and the number of cells that must be suppressed fall after response; pharmacological suppression of residual disease may require less exposure than debulking, as CML dose-reduction studies suggest.
What would test it
Randomised phase 3 non-inferiority trials in two settings (an oral targeted agent in a solid tumour and an ADC) with PFS primary and cumulative toxicity, QoL and cost as secondaries.
Maturity
early clinical
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks

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