title: High-dose cisplatin, etoposide, and cyclophosphamide with autologous stem cell reinfusion in patients with responsive metastatic or high-risk primary breast cancer.
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 chemotherapeutic regimens.
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California 91010.
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
authors.forename: L A
authors.initials: LA
authors.lastname: Leong
authors.forename: K A
authors.initials: KA
authors.lastname: Margolin
authors.forename: R J
authors.initials: RJ
authors.lastname: Morgan
authors.forename: J W
authors.initials: JW
authors.lastname: Raschko
authors.forename: S A
authors.initials: SA
authors.lastname: Akman
authors.forename: C
authors.initials: C
authors.lastname: Ahn
authors.forename: I
authors.initials: I
authors.lastname: Sniecinski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000382:microbiology; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin