PURPOSE: The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival. PATIENTS AND METHODS: Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable. RESULTS: The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy. CONCLUSION: HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.
RCT Entities:
PURPOSE: The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival. PATIENTS AND METHODS: Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable. RESULTS: The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy. CONCLUSION:HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.