ADJUVANT TREATMENT OF BREAST-CANCER - A PILOT IMMUNOCHEMOTHERAPY STUDY WITH CMF, INTERLEUKIN-2 AND INTERFERON-ALPHA

Immune responses, including natural immunity (NI), potentiate the anti tumor effects of chemotherapy. Since interferons and interleukin-2 (IL -2) augment NI, a pilot study was conducted to assess the tolerability and the effects on host immunity of adjuvant chemotherapy associated with IL-2 + interferon alpha (IFN) in breast cancer patients after sur gery. Ten patients underwent alternating 28-day cycles of chemoimmunot herapy [cyclophosphamide + methotrexate + 5-fluorouracil (CMF, days 1, 8) + IL-2 (days 15-19) + IFN (day 22)] and chemotherapy alone (CMF). With this regimen each patient was considered to be a reasonable ''con trol'' of herself. Blood cell count and natural killer cell activity ( NKA) were tested on days 1, 8, 15, 22, and 23. Preliminary in vitro st udies indicated that IL-2 or IFN antagonized the severe inhibition of NKA induced by hydroxy-peroxy-cyclophosphamide (in vitro active deriva tive of cyclophosphamide), alone or associated with methotrexate + 5-f luorouracil. Nine patients completed all six alternating cycles, where as one patient proved to have metastatic lesions after four cycles. Th e protocol was well tolerated, although leukopenia (CMF alone) and leu kopenia with fever and moderate or minimal flu-like symptoms (CMF + IL -2 + IFN) were generally observed. Treatment with IL-2 facilitated com plete recovery of white cell counts and NKA after the nadir on day 15. In conclusion, the present protocol appears to be well tolerated and amenable to administration on an outpatient basis. Therefore, further investigations should be performed to verify whether CMF + IL-2 + IFN would be superior to CMF alone for adjuvant treatment after surgery in breast cancer.