title: Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German Testicular Cancer Study Group.
abstract: OBJECTIVE
  To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features.
  
  
  METHODS
  Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2, ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC.
  
  
  RESULTS
  Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/microL and thrombocytes less than 25,000/microL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively.
  
  
  CONCLUSIONS
  Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.
authors: Department of Oncology, South West German Comprehensive Cancer Center, Eberhard-Karls-University of Tuebingen, Otfried-Mueller-Str 10, 72076 Tuebingen, Germany. joerg.hartmann@med.uni-tuebingen.de
authors: Jörg T
authors: JT
authors: Hartmann
authors: Thomas
authors: T
authors: Gauler
authors: Bernd
authors: B
authors: Metzner
authors: Arthur
authors: A
authors: Gerl
authors: Jochen
authors: J
authors: Casper
authors: Oliver
authors: O
authors: Rick
authors: Marius
authors: M
authors: Horger
authors: Jan
authors: J
authors: Schleicher
authors: Günter
authors: G
authors: Derigs
authors: Regine
authors: R
authors: Mayer-Steinacker
authors: Jörg
authors: J
authors: Beyer
authors: Markus A
authors: MA
authors: Kuczyk
authors: Carsten
authors: C
authors: Bokemeyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000556:secondary; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy*
chemical_list: D005047:Etoposide; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide