5‐fluorouracil with leucovorin in breast cancer

Extensive preclinical data have demonstrated that leucovorin can modulate 5‐fluorouracil (5‐FU) cytotoxicity. Additionally, randomized clinical trials have shown that leucovorin increases the therapeutic index of 5‐FU in patients with advanced colorectal cancer, setting a new therapeutic standard for this disease. Based on this information, several controlled, but nonrandomized, clinical trials have examined the combination of 5‐FU and leucovorin in patients with metastatic breast cancer. Although many of these trials are still ongoing, preliminary information suggests that leucovorin also potentiates 5‐FU activity against breast carcinoma. However, to date, it has not been shown that leucovorin increases the therapeutic index of 5‐FU in these patients. Continued testing of the role of leucovorin in combination chemotherapy for breast cancer appears warranted.