title: TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis.
abstract: OBJECTIVE
  We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.
  
  
  METHODS
  Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.
  
  
  RESULTS
  Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.
  
  
  CONCLUSIONS
  TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
authors.affiliation: Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. feldmand@mskcc.org
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.forename: Joel
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.forename: Patricia
authors.initials: P
authors.lastname: Fischer
authors.forename: Stefan
authors.initials: S
authors.lastname: Turkula
authors.forename: Nicole
authors.initials: N
authors.lastname: Ishill
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Manjit
authors.initials: M
authors.lastname: Bains
authors.forename: Lilian M
authors.initials: LM
authors.lastname: Reich
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D019233:Retreatment; D016879:Salvage Therapy
chemical_list: D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide