title: A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.
abstract: BACKGROUND
  High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT.
  
  
  METHODS
  This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate.
  
  
  RESULTS
  Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81).
  
  
  CONCLUSIONS
  The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens.
  
  
  BACKGROUND
  NCT00231582.
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris. Electronic address: frederic.selle@tnn.aphp.fr.
authors.forename: F
authors.initials: F
authors.lastname: Selle
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: S
authors.initials: S
authors.lastname: Wittnebel
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon.
authors.forename: P
authors.initials: P
authors.lastname: Biron
authors.affiliation: Department of Medical Oncology, Institut Paoli Calmette, Marseille.
authors.forename: G
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Department of Medicine, Institut Bergonié, Bordeaux.
authors.forename: G
authors.initials: G
authors.lastname: Roubaud
authors.affiliation: Department of Medicine, Institut Bergonié, Bordeaux.
authors.forename: B N
authors.initials: BN
authors.lastname: Bui
authors.affiliation: Department of Chemotherapy, Centre Paul Papin, Angers.
authors.forename: R
authors.initials: R
authors.lastname: Delva
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire, Clermont-Ferrand.
authors.forename: J O
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon.
authors.forename: A
authors.initials: A
authors.lastname: Fléchon
authors.affiliation: Department of Medicine, Centre Alexis Vautrin, Nancy.
authors.forename: L
authors.initials: L
authors.lastname: Geoffrois
authors.affiliation: Department of Medicine, Centre Oscar Lambret, Lille.
authors.forename: A
authors.initials: A
authors.lastname: Caty
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris.
authors.forename: D G
authors.initials: DG
authors.lastname: Soares
authors.affiliation: Department of Hematology, Hôpital D'Instruction des Armées Percy, Clamart.
authors.forename: T
authors.initials: T
authors.lastname: de Revel
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris.
authors.forename: J
authors.initials: J
authors.lastname: Gligorov
authors.affiliation: Cytapheresis and Cell Therapy Unit, Hôpital St Louis (AP-HP), Paris.
authors.forename: J M
authors.initials: JM
authors.lastname: Micléa
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris.
authors.forename: C
authors.initials: C
authors.lastname: Dubot
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris.
authors.forename: S
authors.initials: S
authors.lastname: Provent
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris.
authors.forename: I
authors.initials: I
authors.lastname: Temby
authors.affiliation: Statistic, 3ES-Cegedim Strategic Data, Boulogne, France.
authors.forename: M
authors.initials: M
authors.lastname: Gaulet
authors.affiliation: Department of Internal Medicine, Brown University, Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: E
authors.initials: E
authors.lastname: Horn
authors.affiliation: Department of Clinical Research, Hôpital St Louis (AP-HP), Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Brindel
authors.affiliation: Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris.
authors.forename: J P
authors.initials: JP
authors.lastname: Lotz
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D013852:Thiotepa / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015251:Epirubicin; D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide
keywords: TAXIF II trial; germ-cell tumors; hematopoietic stem-cell transplantation; high-dose chemotherapy; nonrefractory patients