Neoadjuvant moderately high-dose chemotherapy with rh-G-CSF in locally advanced breast carcinoma

Aims and background: The poor results of local treatment for locally advanced breast carcinoma (LABC) justify the use of chemotherapy as primary treatment. Retrospective studies have shown a positive correlation between dose and response rate in advanced breast cancer. G-CSF has shown efficacy in achieving optimal dose intensity and ameliorating chemotherapy-induced myelosuppression. The aim of the present study was to assess the efficacy of a moderately high-dose chemotherapy regimen in terms of response rate, disease-free and overall survival and to assess the role of G-CSF in induced neutropenia. Methods: Inclusion criteria were the following: age 2 on day 1), cyclophosphamide (400 mg/m² for 3 consecutive days) and rh-G-CSF (5 μg/kg/die from day 4 to day 12 every 14 days). After mastectomy or quadrantectomy plus radiotherapy, all patients were treated with 4 courses of adjuvant chemotherapy according to the CMF 1-8 schedule (methotrexate, 40 mg/m²; cyclophosphamide, 600 mg/m²; fluorouracil, 600 mg/m²; all on days 1 and 8, with recycle every 4 weeks). Results: From May 1992 to June 1996, 57 patients with histologically proven LABC were preoperatively treated. Forty-four patients were premenopausal and 13 postmenopausal; the median age was 45 years (range, 29-64). Thirty-five patients had stage IIIA and 22 patients stage IIIB disease (7 with inflammatory disease). Forty-seven patients underwent radical mastectomy and 10 conservative surgery. A clinical response was noted in 93% (95% confidence interval, 83-98%) of patients (12% complete responses and 81% partial responses); 2 pathological complete remissions (3.5%) were obtained. No toxic deaths were observed. All patients had a follow-up of at least 42 months. The overall 5-year survival rate was 76% (standard error - SE), 6%) and the 5-year disease-free survival rate was 68% (SE, 6.3%). Conclusions: The 14-day regimen was well tolerated and effective in LABC patients, although not superior to standard-dose chemotherapy. To improve results the use of new drugs in controlled clinical trials seems warranted.