title: First-line high-dose chemotherapy +/- radiation therapy in patients with metastatic germ-cell cancer and brain metastases.
abstract: OBJECTIVE
  To examine the feasibility and efficacy of first-line high-dose chemotherapy (HD-CTX) in patients with advanced metastatic germ-cell tumors (GCT) and brain metastases.
  
  
  METHODS
  Twenty-two patients with brain metastases at initial diagnosis were identified within a cohort of two hundred thirty-one consecutive patients with advanced metastatic disease, entered on a German multicenter trial between January 1993 and July 1998. All patients received first-line HD-CTX with cisplatin-etoposide-ifosfamide (HD-VIP) followed by autologous stem-cell transplantation. Brain irradiation (BRT) with 30-50 Gy +/- 10 Gy boost was applied in patients with symptomatic CNS disease or as consolidation in case of residual CNS lesions after HD-CTX.
  
  
  RESULTS
  A median number of 4 HD-CTX cycles (range 2-5) were applied to the 22 patients. Ten patients received HD-CTX alone and twelve patients were treated with HD-CTX plus BRT. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was seven and five days after each cycle, respectively. Non-hematologic toxicity consisted mainly of mucositis/enteritis (WHO grade 3-4 32%). Two early deaths occurred in twenty-two patients (one CNS-bleeding/one sepsis). Fourteen of twenty patients achieved a CR/PRm- status. Twenty patients (91%) responded in the brain (55% CR/36% PR). Two-year progression-free and overall survival rates were 72% and 81%, respectively. These survival rates are substantially higher compared to the available data in the literature.
  
  
  CONCLUSIONS
  High-dose chemotherapy with autologous stem-cell support +/- BRT appears to be feasible without increased therapy-related mortality in patients with advanced metastatic GCT and brain metastases. The results achieved emphasize the high chemosensitivity of CNS metastases from GCT and suggest a potential role for dose intensification. The dose of BRT in addition to HD-CTX may be tailored to the presence of clinical symptoms and the response of CNS metastases to chemotherapy.
authors.affiliation: Department of Hematology/Oncology, University of Tübingen Medical Center, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: C
authors.initials: C
authors.lastname: Nichols
authors.forename: M
authors.initials: M
authors.lastname: Bamberg
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: N
authors.initials: N
authors.lastname: Schleucher
authors.forename: J
authors.initials: J
authors.lastname: Beyer
authors.forename: P
authors.initials: P
authors.lastname: Schöfski
authors.forename: G
authors.initials: G
authors.lastname: Derigs
authors.forename: U
authors.initials: U
authors.lastname: Rüther
authors.forename: I
authors.initials: I
authors.lastname: Böhlke
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005833:Genital Neoplasms, Female / Q000473:pathology*; D005834:Genital Neoplasms, Male / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide