Leucovorin in combination chemotherapy of breast cancer

Cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone were administered for 165, 28-day cycles to 33 patients with metastatic breast cancer. Because of serious infections (fever larger than or equal to 101 degrees F. granulocytes less than 1,000/mm, 3 and hospitalization) and 1 drug death in the first 4 patients, oral calcium leucovorin, 20 to 30 mg/m2 orally, was given 2 days after methotrexate in subsequent treatment cycles. There were 26 cycles without calcium leucovorin and 6 serious infections; 139 cycles with calcium leucovorin and 5 serious infections (p = 0.002). Objective response was seen in 13 of 18 evaluable patients with no previous treatment and in only 2 of 11 patients with previous treatment (p = 0.0065). Equivalent doses were given to all subsets of patients. It is concluded that leucovorin added to the above combination of drugs can preserve antitumor activity while decreasing serious infections and that prior therapy significantly decreases the response rate to this combination.