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This combination chemotherapy regimen was investigated by the University of Erlangen-Nürnberg Medical School in the CAO/ARO/AIO-04 Phase 3 trial for the treatment of locally advanced rectal cancer. The regimen incorporates oxaliplatin into the standard preoperative fluorouracil-based chemoradiotherapy and postoperative fluorouracil chemotherapy. Fluorouracil (5-FU) is a pyrimidine analog that acts as an antimetabolite, primarily inhibiting thymidylate synthase to disrupt DNA synthesis. Oxaliplatin is a platinum-based antineoplastic agent that forms reactive platinum complexes which bind to DNA, creating intra- and inter-strand cross-links that inhibit DNA replication and transcription. Leucovorin (calcium folinate) is included in the adjuvant phase as a biochemical modulator to enhance the binding of 5-FU to thymidylate synthase, thereby increasing its cytotoxic effect. The trial demonstrated that the addition of oxaliplatin improved disease-free survival compared to 5-FU alone.
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