title: A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours.
abstract: BACKGROUND
  The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population.
  
  
  METHODS
  Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow-up of 1 year.
  
  
  RESULTS
  Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy.
  
  
  CONCLUSIONS
  Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation.
authors.affiliation: The Department of Medical Oncology, St Bartholomew's Hospital, London, UK. jonathan.shamash@bartsandthelondon.nhs.uk
authors.forename: J
authors.initials: J
authors.lastname: Shamash
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.forename: K
authors.initials: K
authors.lastname: Mutsvangwa
authors.forename: P
authors.initials: P
authors.lastname: Wilson
authors.forename: W
authors.initials: W
authors.lastname: Ansell
authors.forename: E
authors.initials: E
authors.lastname: Walsh
authors.forename: D
authors.initials: D
authors.lastname: Berney
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
authors.forename: T
authors.initials: T
authors.lastname: Oliver
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D000077150:Oxaliplatin; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin