Dose Intensification of Chemotherapy in Advanced Breast Cancer: A Feasibility Phase II Study

Abstract

Aims and background Dose intensification of chemotherapy is associated with increased response rates in advanced breast cancer. Achievement of dose incrementation is usually limited by drug-dependent bone marrow toxicity. The recent availability of recombinant human colony-stimulating factors (CSFs) have made it possibile to evaluate their potential in ameliorating chemoterapy-induced myelosuppression. The aim of this study was to evaluate tolerability and effectiveness of an intensified mitoxantrone, methotrexate and mitomycin-C (3M) regimen, given with G-CSF support in patients with advanced breast cancer (ABC). Study design Twenty-eight eligible patients with advanced breast cancer were treated with mitomycin -C (7 mg/sqm iv every 4 weeks), methotrexate (35 mg/sqm iv) and mitoxantrone (7 mg/sqm iv every 2 weeks) for 6 cycles. Recombinant human granulocyte colony-stimulating factor (r-HuG-CSF, Filgrastim) (5 μg/kg/day) was given subcutaneously from day 2 to day 12 after each chemotherapy administration to prevent leukopenia. Results Of the 27 evaluable patients, 4 had complete response and 14 achieved partial response; the overall response rate was 63% (95% Cl; 46.8%-82.2%). The median duration of response was 8 months (range, 4-13+). Chemotherapy-related toxicity was mild: only 3 out of 163 courses had to be postponed due to myelotoxicity. Conclusions The 3M regimen given at 2- week intervals is a feasible, active and well toleratel treatment in patients not previously treated for metastatic breast cancer.