High-dose cyclophosphamide, etoposide and carboplatin with autologous bone marrow support for metastatic breast cancer: long-term results

Abstract

Summary:We report long-term results of high-dose cyclophosphamide, etoposide and carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two patients. Twelve patients had received adjuvant chemotherapy. Predominant sites of metastases were lung (eight), chest wall (four), liver (four), bone (three) and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR) in four patients, partial (PR) in 10 patients and stable (SD) in five patients. After high-dose chemotherapy eight patients were in CR, six PR, four SD and one progressive disease. Two patients died of regimen-related toxicities (candidal sepsis and alveolar hemorrhage). With a median follow-up period of 55 months (minimum 48 months), 12 patients have died of recurrent breast cancer, one died of toxicity of salvage chemotherapy, two are alive with disease, two are alive and free of progressive disease. One patient with relapsed disease was lost to follow-up. Median event-free survival is 6 months and median overall survival is 17 months. All three of the long-term disease-free survivors had predominantly nodal disease. Two of these three patients presented with metastatic disease and received high-dose chemotherapy with ABMT as part of initial therapy for breast cancer; two of three attained CR to standard-dose cytoreductive therapy; none received doxorubicin-containing adjuvant chemotherapy. Keywords: high-dose chemotherapy; metastatic breast cancer; autologous bone marrow transplantation High-dose chemotherapy with autologous stem cell support is commonly used to treat metastatic adenocarcinoma of the breast. Such therapy is considered by many to be effective therapy for metastatic breast cancer despite the attendant risks, expense, and minimal evidence of long-term benefit.From 1990 to 1993 we treated 20 women with metastatic breast cancer with a unique high-dose combination of cyclophosphamide, etoposide and carboplatin supported by autologous bone marrow infusion. In general, ours was a poor risk group of patients, five of whom had no response to pretransplant cytoreductive therapy. With a minimum follow-up time of 4 years, we now present mature results of this high-dose regimen. Materials and methodsPatients with metastatic breast cancer who had at least a stable disease response to most recent standard-dose (cytoreductive) chemotherapy were eligible for this study. All patients had either progressed on hormonal therapy or had estrogen receptor-negative tumors. All patients were required to have an ECOG performance status of 0-2 and have adequate end-organ function including serum creatinine р2.0 mg/dl, total bilirubin р2.0 mg/dl, FEV 1 , FVC and DLCO Ͼ 60% of predicted values, left ventricular ejection fraction Ͼ45% by MUGA or echocardiography and WBC Ͼ 4.0 × 10 9 /l and platelets Ͼ 100 × 10 9 /l. Patients with central nervous system metastases or metastases confined to bone only were excluded. Other pertinent patient characterist...

High dose chemotherapy and autologous blood stem cell support in women with breast carcinoma and isolated supraclavicular lymph node metastases

“…Despite excision, radiation therapy, and systemic therapy, the 5‐year DFS for women with SCN recurrence remains as low as 10–24% 2, 7, 10. Both registry data and the results of a number of Phase II trials indicate that such patients, who possess a minimal micrometastatic disease burden, have a more favorable outcome after high dose CT (HDCT) 11, 12. In particular, patients with limited metastatic sites who can be rendered as having “no evidence of disease” (NED) after surgery or radiation therapy appear to have the best prognosis 13, 14.…”