title: Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial.
abstract: BACKGROUND
  The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate <50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study.
  
  
  METHODS
  The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 μg/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used.
  
  
  RESULTS
  Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression.
  
  
  CONCLUSIONS
  In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate.
  
  
  BACKGROUND
  NCT00127049.
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.forename: G
authors.initials: G
authors.lastname: Gravis
authors.forename: A
authors.initials: A
authors.lastname: Flechon
authors.forename: L
authors.initials: L
authors.lastname: Geoffrois
authors.forename: C
authors.initials: C
authors.lastname: Chevreau
authors.forename: B
authors.initials: B
authors.lastname: Laguerre
authors.forename: R
authors.initials: R
authors.lastname: Delva
authors.forename: J C
authors.initials: JC
authors.lastname: Eymard
authors.forename: F
authors.initials: F
authors.lastname: Rolland
authors.forename: N
authors.initials: N
authors.lastname: Houede
authors.forename: A
authors.initials: A
authors.lastname: Laplanche
authors.forename: D
authors.initials: D
authors.lastname: Burcoveanu
authors.forename: S
authors.initials: S
authors.lastname: Culine
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D011446:Prospective Studies; D016879:Salvage Therapy; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D007069:Ifosfamide; D000093542:Gemcitabine
keywords: chemotherapy; gemcitabine; germ-cell tumor; salvage