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FLOT + simvastatin is an investigational combination regimen being evaluated in the RESTAGE trial for the treatment of resectable gastroesophageal adenocarcinoma. The regimen adds simvastatin, a small molecule HMG-CoA reductase inhibitor (statin), to the standard-of-care perioperative chemotherapy regimen FLOT. FLOT consists of 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel. While FLOT targets DNA synthesis and microtubule dynamics to induce tumor cell death, simvastatin is repurposed for its potential to inhibit the mevalonate pathway, which may disrupt tumor cell proliferation and survival. The McGill University Health Centre is the lead sponsor for the Phase II study assessing whether this addition improves outcomes compared to standard chemotherapy alone.
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