Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial.

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement. Patients who responded were significantly older (p = 0.05) than nonresponders. Dose escalation in eight patients did not result in any clear evidence of additional responses. Major toxicities were fatigue, anorexia with weight loss, and reversible leukopenia (less than 3.5 x 10(9) leukocytes/L in 16 patients). Natural killer cell and antibody-dependent cell-mediated cytotoxicity were significantly (p less than 0.05) enhanced 48 hours after interferon administration began but subsequently declined despite continued therapy. Serum beta 2-microglobulin concentration increased on day 15 (p less than 0.05) and remained significantly elevated on day 22 (p less than 0.005). Peak interferon titers (mean, 62 U) occurred 6 hours after interferon was started, varied widely between patients, and were higher and more persistent with dose escalation. Once an optimal dose is defined, prospectively randomized trials will define what role interferons may have in systemic therapy of breast carcinoma.