Background: A dose response relationship for doxorubicin and cyclophosphamide has been suggested. In a previous dose finding study we treated advanced breast cancer patients with escalating doses of doxorubicin and cyclophosphamide in combination with GM-CSF. The aim of this study is to further define the acute and cumulative toxicity of this treatment in relation to its antitumor activity.
Patients and methods: Twenty-eight patients with metastatic breast cancer were treated with doxorubicin (90 mg/m2) and cyclophosphamide (1000 mg/m2) at 3-week intervals. Dose reductions of 10% were applied in the second and fourth cycles. On the second day GM-CSF was started at 250 mu g/m2 daily for 10 days. The intention was to give 6 cycles, but when a complete remission was reached earlier only one more cycle was given as consolidation.
Results: The median number of cycles was 5 (range 2-6). Twenty-three patients responded (82%, 95% CI 69%-97%), with 9 of them achieving a complete response (32%, 95% CI 14%-50%). For the 18 patients evaluable for time to progression and survival the median time to progression was 8 months and the median survival 14.5 months. Toxicity was substantial: grades 3 or 4 neutropenia occurred in 95% of cycles and grades 3-4 thrombocytopenia in 49% of cycles. Grade 3-4 mucositis was present in 13% of the cycles. Weakness and fatigue were always present and were cumulative. Four patients had a decline in the left ventricular ejection fraction (LVEF). These side effects were the reason for discontinuing therapy in 9 of the 28 patients (32%).
Conclusion: This treatment has a high response rate in comparison with conventional-dose chemotherapy but does not prolong time to progression or survival. The toxicity makes this protocol unsuitable for use as palliative treatment.