Loading
Giving a targeted drug in pulses rather than continuously might slow the emergence of resistant cells and reduce side effects. Early results are mixed, so this needs careful trials with clear rules for when to try it.
Randomised trials of intermittent versus continuous dosing of targeted agents, selected by biology: intermittent schedules are favoured where preclinical data show drug-addicted resistant clones (as in some BRAF-mutant melanoma models) or where toxicity is exposure-driven; disfavoured where continuous suppression is needed. The SWOG S1320 trial found intermittent BRAF/MEK inhibition did not improve PFS in melanoma, so the proposal targets settings with stronger mechanistic support (e.g., some hormonal and ALK-driven settings) and uses ctDNA to define pulse timing.
One of the most cited trial reports Europe PMC returns for BRAF in Melanoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
One of the most cited trial reports Europe PMC returns for ALK in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
BRAF testing became mandatory in advanced melanoma and vemurafenib the first approved BRAF inhibitor; combination with MEK inhibitors soon replaced monotherapy.
Shares COMBI-d, BRAF, Melanoma, Small-molecule kinase inhibitors.
Shares Wrong doses, Drug resistance (primary and acquired), Acquired resistance to every therapy, Circulating tumour DNA (ctDNA).
Shares BRIM-3: improved survival with vemurafenib in melanoma with BRAF V600E mutation, Melanoma.
Shares COLUMBUS, BRAF, Melanoma, Small-molecule kinase inhibitors.
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy, Melanoma, Non-small-cell lung cancer.
Shares Wrong doses, Drug resistance (primary and acquired), Acquired resistance to every therapy, Melanoma.