HIGH-DOSE CISPLATIN, ETOPOSIDE, AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS STEM-CELL REINFUSION IN PATIENTS WITH RESPONSIVE METASTATIC OR HIGH-RISK PRIMARY BREAST-CANCER

Background. This study was designed to establish the feasibility of co mbining high-dose cisplatin, etoposide, and cyclophosphamide followed by stem cell rescue in patients with responsive metastatic or high-ris k primary breast cancer.Methods. Eligibility criteria included the pre sence of high-risk primary breast cancer (Stage II with 10 or more inv olved axillary nodes or Stage IIIA or B) or Stage IV disease in comple te 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 ci splatin (50-150 mg/m(2) 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 wi thout peripheral stem cells, or granulocyte colony-stimulating factor primed peripheral stem cells alone were reinfused. Results. Thirty pat ients were enrolled in this study. Twenty-eight patients demonstrated no evidence of persistent renal damage after treatment. Two patients s uffered symptomatic peripheral neuropathy, and one patient required a hearing aid 3 months after therapy. Hematopoietic toxicities were acce ptable. There were two fatalities; Streptococcus viridans bacteremia a nd adult respiratory distress syndrome developed in one patient; and o ne patient who received 262 mg/m(2) of cisplatin died of renal failure . Twelve of 18 assessable patients with Stage IV disease are without e vidence 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 pri mary breast cancer are without evidence of disease. Conclusions. The P hase II dose of cisplatin when given on a day -12 and day -5 schedule in combination with etoposide and cyclophosphamide has been establishe d at a total of 250 mg/m(2). Dose-limiting toxicity has been defined a s renal failure, and response rates were comparable to previously repo rted high-dose chemotherapeutic regimens.