title: Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors.
abstract: OBJECTIVE
  The efficacy and tolerability of M-TIP was evaluated as first-line treatment for patients with poor-risk germ cell tumors (GCT), according to International Germ Cell Cancer Collaborative Group (IGCCCG) criteria.
  
  
  METHODS
  Thirty patients with poor-risk GCT were treated with M-TIP (methotrexate 250 mg/m(2) given as a 4-hour infusion with folinic acid rescue on day 1, paclitaxel 175 mg/m(2) given as a 3-hour infusion on day 1, followed by ifosfamide 1.2 g/m(2) given as a 2-hour infusion and cisplatin 20 mg/m(2) given as a 2-hour infusion on days 2 to 6) regimen for four cycles.
  
  
  RESULTS
  Five (16.6%, 95% confidence interval [CI]: 2%-31%) patients achieved clinical complete response (cCR) with chemotherapy only, 15 (50%, 95% CI: 31-69%) patients pathologic complete response (pCR) (11 had necrosis/fibrosis and 4 had mature teratoma) and 3 (10%) patients surgical complete response (sCR) for an overall favorable response of 76.6%. Twenty-one patients are continuously disease-free at a median follow-up of 5.3 years (range 0.9-8.4+ years), resulting in a 5-year progression-free survival (PFS) rate of 66.6% (95% CI = 49%-85%) and a 5-year survival rate of 70% (95% CI = 53%-87%). Toxicity was generally mild except for myelotoxicity. Patients with febrile neutropenia were successfully treated with broad spectrum antibiotics and G-CSF support. Hematologic toxicity in this trial was ameliorated with the use of G-CSF. Neurotoxicity and nephrotoxicity were not a problem, since only 6.6% and 3.3% of patients developed sensory neuropathy and renal toxicity, respectively.
  
  
  CONCLUSIONS
  M-TIP is a highly effective (high proportion of patients achieved long-term disease-free status, lack of relapses) and well tolerated regimen for first-line treatment of poor-risk GCT patients. These results have to be compared with the standard BEP chemotherapy or more intensive regimens in multicentre randomized trials.
authors.affiliation: Second Department of Internal Medicine, Propaedeutic, Oncology Section, University of Athens, Attikon University Hospital, Athens, Greece. pectasid@otenet.gr
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Eirini
authors.initials: E
authors.lastname: Pectasides
authors.forename: George
authors.initials: G
authors.lastname: Papaxoinis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Xiros
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kamposioras
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tountas
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate