Dose-intensive chemotherapy with doxorubicin, cyclophosphamide and GM-CSF fails to improve survival of metastatic breast cancer patients

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Abstract
A dose response relationship for doxorubicin and cyclophosphaniide has been suggested. In a previous dose finding study we treated advanced breast cancer padents with escalating doses of doxorubicin and cyclophos phaniide lit 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. Twenty-eight patients with metastatic breast cancer were treated with doxorubiciri (90 mg/ m and cyclophosphamide (1000 mg/m 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 sg/m 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. 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 (3 2%, 95% CL 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 cumula tive. 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 (3 2%). 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 paffiative treatment.

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