title: A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.
abstract: One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments.
  
  
  
  Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival.
  
  
  
  With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment.
  
  
  
  Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.
authors: Institute of Oncology "Prof Dr Ion Chiricuta", Department of Radiotherapy-Medical Oncology, Cluj Napoca, Romania.
authors: Cristina
authors: C
authors: Ligia Cebotaru
authors: Nicoleta
authors: N
authors: Zenovia Antone
authors: Elena
authors: E
authors: Diana Olteanu
authors: Nona
authors: N
authors: Bejinariu
authors: Rares
authors: R
authors: Buiga
authors: Nicolae
authors: N
authors: Todor
authors: Dana
authors: D
authors: Ioana Iancu
authors: Tudor
authors: T
authors: Eliade Ciuleanu
authors: Viorica
authors: V
authors: Nagy
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004264:DNA Topoisomerases, Type I / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D004720:Endonucleases / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D000951:Antigens, Neoplasm; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004720:Endonucleases; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C508053:ERBB2 protein, human; C071447:ERCC1 protein, human; C528909:TOP1 protein, human