High-dose induction chemotherapy of metastatic breast cancer in protected environment: a prospective randomized study.

To test the hypothesis of whether high doses of chemotherapy in combination achieve higher response rates and longer durations of response and survival, we treated 33 pre- and perimenopausal patients with good performance status in a prospective trial with escalating doses of fluorouracil, doxorubicin and cyclophosphamide (FAC). Patients were randomly assigned to be treated within a protected environment (laminar air flow room), with prophylactic antibiotics, or in a standard hospital room. Important patient characteristics were equally distributed in the two treatment arms. A major objective response was observed in 27 of the 32 evaluable patients (84%), and 11 (34%) achieved a complete remission (CR). There was no significant difference in overall and complete response rates between the two treatment arms, nor was there a substantial difference in times to progression or survival between the groups treated in or out of the protected environment. Comparison of the results of this study with previously reported programs of FAC chemotherapy in patients with metastatic breast cancer shows that this study achieved higher overall and complete response rates. However, neither the time to progression, nor the survival of responders or the entire patient group was different from our previous experience with standard FAC chemotherapy. When the study was initiated in 1976, the proposed dose escalation represented high-dose chemotherapy. In retrospect, even the "high" doses used in this study represent only a modest increase over standard doses of chemotherapy. Much steeper dose escalations will be needed to evaluate the efficacy of high-dose chemotherapy in breast cancer, as well as the protective value of the protected environment and prophylactic antibiotics in metastatic breast cancer.