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This combination chemotherapy and hormonal regimen consists of cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, and triiodothyronine. Historically investigated by the Western Cancer Study Group (WCSG) in the late 1970s and early 1980s, the protocol was designed for the treatment of advanced breast cancer. The regimen combines the cytotoxic mechanisms of alkylating agents (cyclophosphamide) and antimetabolites (methotrexate and 5-fluorouracil) with the anti-inflammatory and lympholytic effects of corticosteroids (prednisone). The addition of triiodothyronine was based on early hypotheses that thyroid hormones could modulate tumor growth or enhance the efficacy of chemotherapy. Clinical trials demonstrated that while this combination increased response rates compared to sequential single-agent therapy, it did not significantly improve overall survival for the majority of patients, with the exception of those with liver involvement.
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