Prolonged disease-free survival in advanced breast cancer treated with "super-CMF" adriamycin: an alternating regimen employing high-dose methotrexate with citrovorum factor rescue.

Sixty-six patients were treated with the combination "super-CMF" as follows: cyclophosphamide 100 mg/m2 po days 2 through 14; methotrexate 3.0 g/m2 iv days 1 and 8; 5-fluorouracil 600 m g/m2 iv days 1 and 8; citrovorum factor rescue 10 mg/m2 iv days 2 and 9 and po days 2 through 4 and 9 through 11; and Adriamycin 70 to 90 mg/m2 iv day 29. This cycle was repeated at 49-day intervals. The single-agent activity of high-dose methotrexate with rescue was first evaluated in breast cancer patients in a truncated phase II study; 3 of 19 had a partial response (greater than 50% regression of measurable lesions) after 2 to 6 weekly courses and another 6 to 19 had some objective evidence of response (greater than 25%, less than 50%). The response rate to the combination "super-CMF" was: complete response (CR) 15 of 55 evaluable patients (27%) and partial response (PR) 28 of 55 (51%). The median duration of response was 24.5 months and the median time to treatment failure was 21.6 months. Nineteen of these patients have completed 12 to 18 months of drug treatment and have been followed in continuing remission for 1 to 28 months without further therapy. The total response rate and the CR rate achieved with this regimen are substantial, and the durability of the responses appears to be considerably greater than that obtained with other drug combinations.