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This multimodal metronomic chemotherapy regimen is being evaluated by the Centre Hospitalier Universitaire de Besançon in the REPROGRAM-02 Phase II/III trial for the treatment of metastatic colorectal cancer (mCRC). The regimen consists of a two-month induction phase combining the multi-kinase inhibitor regorafenib with metronomic doses of capecitabine (625 mg/m² twice daily) and cyclophosphamide (50 mg daily), supplemented with low-dose aspirin (75 mg daily). This approach utilizes continuous low-dose administration of cytotoxic agents to achieve anti-tumor effects, anti-angiogenic activity, and immune system stimulation with improved tolerance compared to standard dosing. The strategy is designed as a sequential treatment to be administered before standard second-line chemotherapy (such as FOLFIRI or FOLFOX) to improve response rates and overall survival in patients who have progressed after first-line therapy.
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