title: Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide.
abstract: OBJECTIVE
  To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide (VIP), or vinblastine (VeIP), in patients with recurrent germ cell tumors.
  
  
  METHODS
  Nonrandomized, prospective phase II trial.
  
  
  METHODS
  Tertiary referral university hospital.
  
  
  METHODS
  Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular (46 patients), ovarian (1 patient), and extragonadal (9 patients) origin were evaluable for response after not being cured with cisplatin, vinblastine, and etoposide regimens.
  
  
  METHODS
  Patients were administered cisplatin (20 mg/m2 body surface area daily for 5 days), ifosfamide (1.2 g daily for 5 days), plus either etoposide (75 mg daily for 5 days) or vinblastine (0.11 mg/kg body weight on days 1 and 2). In addition, vigorous intravenous hydration therapy with normal saline (100 to 125 mL/h) was administered during the treatment course. Uroepithelial protective agents, N-acetylcysteine (orally) or mesna (intravenously), were administered. Four courses were administered to responding patients every 3 weeks. When complete excision was feasible, surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy.
  
  
  RESULTS
  Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone, whereas 8 additional patients were free of disease after resection of teratoma (3 patients) or carcinoma (5 patients) for a total disease-free rate of 36% (95% CI, 23.4 to 49.6). The 95% CI median duration of remission for these patients is 34 months (range, 3 to more than 42; 95% CI, 9 months to infinity), and the median survival for all eligible patients is 12.7 months (95% CI, 10 months to 26 months), with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more. Nine of fifty-eight patients remain free of disease, including 7 patients for 2 years or longer. Hematologic and nephrotoxicity were the predominant drug-related toxicities, with one drug-related death secondary to pneumonia.
  
  
  CONCLUSIONS
  Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors.
authors.affiliation: Indiana University School of Medicine, Indianapolis.
authors.forename: P J
authors.initials: PJ
authors.lastname: Loehrer
authors.forename: R
authors.initials: R
authors.lastname: Lauer
authors.forename: B J
authors.initials: BJ
authors.lastname: Roth
authors.forename: S D
authors.initials: SD
authors.lastname: Williams
authors.forename: L A
authors.initials: LA
authors.lastname: Kalasinski
authors.forename: L H
authors.initials: LH
authors.lastname: Einhorn
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide