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.
- 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.
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