title: Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer.
abstract: OBJECTIVE
  To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs).
  
  
  METHODS
  Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m(2), and cisplatin 100 mg/m(2) were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m(2); the largest dose was selected for the phase II part of the trial.
  
  
  RESULTS
  Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity.
  
  
  CONCLUSIONS
  Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.
authors.affiliation: Department of Medicine, Joan and Sanford I Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: J
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: M
authors.initials: M
authors.lastname: Mazumdar
authors.forename: M
authors.initials: M
authors.lastname: Bains
authors.forename: T
authors.initials: T
authors.lastname: Mariani
authors.forename: J
authors.initials: J
authors.lastname: Bacik
authors.forename: D
authors.initials: D
authors.lastname: Bajorin
authors.forename: G J
authors.initials: GJ
authors.lastname: Bosl
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D018237:Germinoma / Q000188:drug therapy* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016879:Salvage Therapy; D043823:Taxoids; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide