High‐dose cisplatin, etoposide, and cyclophosphamide with autologous stem cell reinfusion in patients with responsive metastatic or high‐risk primary breast cancer

G. Somlo, J. H. Doroshow, S. J. Forman, L. A. Leong, K. A. Margolin, R. J. Morgan, J. W. Raschko, S. A. Akman, C. Ahn, I. Sniecinski

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38 Scopus citations

Abstract

Background. This study was designed to establish the feasibility of combining high‐dose cisplatin, etoposide, and cyclophosphamide followed by stem cell rescue in patients with responsive metastatic or high‐risk primary breast cancer. Methods. Eligibility criteria included the presence of high‐risk primary breast cancer (Stage II with 10 or more involved axillary nodes or Stage IIIA or B) or Stage IV disease in complete or partial response; physiologic age 50 years or younger; Karnofsky performance status of 80% or greater; and creatinine clearance of 80 ml/minute or greater. Chemotherapy consisted of escalating doses of cisplatin (50–150 mg/m2 intravenously [IV]) given on days –‐12 and –‐5, etoposide (30 mg/kg IV) given on days –‐12 and –‐5, and cyclophosphamide (100 mg/kg IV) on day –‐3. On day 0, autologous bone marrow with or without peripheral stem cells, or granulocyte colony‐stimulating factor primed peripheral stem cells alone were reinfused. Results. Thirty patients were enrolled in this study. Twenty‐eight patients demonstrated no evidence of persistent renal damage after treatment. Two patients suffered symptomatic peripheral neuropathy, and one patient required a hearing aid 3 months after therapy. Hematopoietic toxicities were acceptable. There were two fatalities; Streptococcus viridans bacteremia and adult respiratory distress syndrome developed in one patient; and one patient who received 262 mg/m2 of cisplatin died of renal failure. Twelve of 18 assessable patients with Stage IV disease are without evidence of progression; 3 of these patients are progression‐free at 11+, 12+, and 32+ months. With a median follow‐up of 16+ months (range, 4–31 months), 7 patients of the group of 11 treated with high‐risk primary breast cancer are without evidence of disease. Conclusions. The Phase II dose of cisplatin when given on a day –‐12 and day ‐‐‐5 schedule in combination with etoposide and cyclophosphamide has been established at a total of 250 mg/m2. Dose‐limiting toxicity has been defined as renal failure, and response rates were comparable to previously reported high‐dose chemother‐apeutic regimens.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalCancer
Volume73
Issue number1
DOIs
StatePublished - Jan 1 1994

Keywords

  • autologous stem cell support
  • breast cancer
  • cisplatin
  • cyclophosphamide
  • etoposide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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