title: High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.
abstract: OBJECTIVE
  This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer.
  
  
  METHODS
  Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response.
  
  
  RESULTS
  The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%).
  
  
  CONCLUSIONS
  High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.
authors.affiliation: Universitätsklinikum Rudolf Virchow, Abteilung für Innere, Medizin mit Schwerpunkt Hämatologie und Onkologie, Freie Universität Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Siegert
authors.forename: J
authors.initials: J
authors.lastname: Beyer
authors.forename: I
authors.initials: I
authors.lastname: Strohscheer
authors.forename: H
authors.initials: H
authors.lastname: Baurmann
authors.forename: H
authors.initials: H
authors.lastname: Oettle
authors.forename: J
authors.initials: J
authors.lastname: Zingsem
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: D
authors.initials: D
authors.lastname: Huhn
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018237:Germinoma / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide