Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: Five-year follow-up

Purpose: To determine the safety and efficacy of multiple cycles of dose-in tensive, nonablative chemotherapy in women with poor-prognosis breast cance r. Patients and Methods: Women with stage II breast cancer and 10 or more invo lved nodes or four or more involved nodes and estrogen receptor-negative tu mors and women with stage III disease received three cycles of epirubicin 2 00 mg/m(2) and cyclophosphamide 4 g/m(2), with progenitor cell and filgrast im support every 28 days (n = 79) or 21 days (n = 20), patients were review ed at least twice yearly thereafter. Twenty-six patients had bone marrow an d apheresis collections assessed for the presence of micrometastatic tumor cells. Results: Ninety-nine women (median age, 43 years; range, 24 to 60 years) we re treated. Ninety-two completed all three cycles of chemotherapy, The majo r toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given trea tment every 28 days and those treated every 21 days. Febrile neutropenia oc curred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles bur tended to be short-lived and was reversible. The card iac ejection fraction fell by a median of 4% during treatment, and three pa tients developed evidence of cardiac failure after chemotherapy. Two patien ts (2%) died of acute toxicity Three of 26 patients had evidence of circula ting micrometastatic tumor cells. The actuarial distant disease-free and ov erall survival races at 60-month follow-up were 64% (95% confidence interva l [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. Conclusion: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to t hose in other studies of myeloablative chemotherapy in poor-prognosis breas t cancer. The regimen is being evaluated in a randomized trial of the Inter national Breast Cancer Study Group. J Clin Oncol 17:82-92. (C) 1999 by American Society of Clinical Oncology.