Ninety evaluable metastatic breast cancer patients refractory to hormonal therapy and combinations of cyclophosphamide, methotrexate, 5-fluorouracil, and doxorubicin were treated with a low-dose mitomycin regimen, i.e., 10 mg/m2 intravenously every 28 days. In order to minimize thrombocytopenia, dose de-escalations related to platelet counts were made. One patient (1%) had a complete response and 17% had partial responses for a median duration of 4 months. The time to progression for the responders and stabilized patients was similar; however, the responders and stabilized patients lived significantly longer than did the progressors. Hematologic toxicity was minimized because of planned de-escalations in mitomycin dosage. Perivenous ulceration, both immediate and delayed (8%), congestive heart failure (2%), and heart-renal failure with malignant hypertension (2%) resulted in significant morbidity, including two drug-related deaths. Although mitomycin dosages were successfully titrated according to platelet counts in this group of chemotherapy-refractory patients, prolonged use of this drug in adjuvant or early metastatic breast cancer patients is not recommended because of potentially irreversible thrombocytopenia.
Cancer 51:1034-1040. 1983.
HE MOST effective chemotherapeutic agents in the T management of metastatic breast carcinoma are doxorubicin (Adriamycin), cyclophosphamide, methotrexate, 5-fluorouracil (SFU), vincnstine, and prednisone. When various combinations of these drugs have been exhausted, the effectiveness of other chemotherapy treatments has been disappointing. In order to prolong the lives of patients with metastatic breast cancer, new drugs must be developed and tested.
In initial clinical trials, mitomycin was usually given intravenously for five or six consecutive days and then every day or two until the patient received 20 mg/m' or until hematologic toxicity occurred. Although mi-