DOSE-INTENSIVE CHEMOTHERAPY WITH DOXORUBICIN, CYCLOPHOSPHAMIDE AND GM-CSF FAILS TO IMPROVE SURVIVAL OF METASTATIC BREAST-CANCER PATIENTS

Background: A dose response relationship for doxorubicin and cyclophos phamide has been suggested. In a previous dose finding study we treate d advanced breast cancer patients with escalating doses of daxorubicin and cyclophosphamide in combination with GM-CSF. The aim of this stud y is to further define the acute and cumulative toxicity of this treat ment in relation to its antitumor activity. Patients and methods: Twen ty-eight patients with metastatic breast cancer were treated with doxo rubicin (90 mg/m(2)) and cyclophosphamide (1000 mg/m(2)) at 3-week int ervals. Dose reductions of 10% were applied in the second and fourth c ycles. On the second day GM-CSF was started at 250 mu g/m(2) daily for 10 days. The intention was to give 6 cycles but when a complete remis sion was reached earlier only one more cycle was given as consolidatio n. Results: The median number of cycles was 5 (range 2-6). Twenty-thre e patients responded (82%, 95% CI 69%-97%), with 9 of them achieving a complete response (32%, 95% CI 14%-50%). For the 18 patients evaluabl e for time to progression and survival the median time to progression was 8 months and the median survival 14.5 months. Toxicity was substan tial: 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 wer e cumulative. Four patients had a decline in the left ventricular ejec tion fraction (LVEF). These side effects were the reason for discontin uing therapy in 9 of the 28 patients (32%). Conclusion: This treatment has a high response rate in comparison with conventional-dose chemoth erapy but does not prolong time to progression or survival. The toxici ty makes this protocol unsuitable for use as palliative treatment.