title: Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes.
abstract: BACKGROUND
  Since 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over the original regimen.
  
  
  METHODS
  Patients received four cycles of ifosfamide at 2.5 g/m(2) on days 1-2, etoposide, and cisplatin at 100 and 33 mg/m(2), respectively, on days 3-5 every 21 days, followed by surgery. Results were stratified according to the International Germ Cell Consensus Classification Group-2 (IGCCCG-2).
  
  
  RESULTS
  From February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm-). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4-232.0). Two-year progression-free and 5-year overall survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively. Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3-4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded.
  
  
  CONCLUSIONS
  Dose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage setting.
authors.affiliation: Departments of Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Necchi
authors.forename: N
authors.initials: N
authors.lastname: Nicolai
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.forename: D
authors.initials: D
authors.lastname: Raggi
authors.forename: E
authors.initials: E
authors.lastname: Farè
authors.forename: P
authors.initials: P
authors.lastname: Giannatempo
authors.forename: M
authors.initials: M
authors.lastname: Catanzaro
authors.forename: D
authors.initials: D
authors.lastname: Biasoni
authors.forename: T
authors.initials: T
authors.lastname: Torelli
authors.forename: S
authors.initials: S
authors.lastname: Stagni
authors.forename: A
authors.initials: A
authors.lastname: Milani
authors.forename: L
authors.initials: L
authors.lastname: Piva
authors.forename: G
authors.initials: G
authors.lastname: Pizzocaro
authors.forename: A M
authors.initials: AM
authors.lastname: Gianni
authors.forename: R
authors.initials: R
authors.lastname: Salvioni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide
keywords: combination chemotherapy; salvage therapies; testicular neoplasms