title: The efficacy of irinotecan, paclitaxel, and oxaliplatin (IPO) in relapsed germ cell tumours with high-dose chemotherapy as consolidation: a non-cisplatin-based induction approach.
abstract: OBJECTIVE
  To determine the outcome of an expanded cohort of patients with relapsed germ cell tumours (GCTs) treated with a salvage chemotherapy regimen consisting of irinotecan, paclitaxel and oxaliplatin (IPO) and assess the role of IPO as an alternative to standard cisplatin-based chemotherapy regimens in this setting.
  
  
  METHODS
  The results of 72 consecutive patients were reviewed retrospectively. IPO was used either as a second-line treatment (29 patients), of which 20 patients subsequently received high-dose chemotherapy (HDCT), or third-line (43), of which 32 patients proceeded to HDCT.
  
  
  RESULTS
  The 2-year progression-free survival (PFS) and 3-year overall survival (OS) rates for the whole cohort were 30.2% (95% confidence interval [CI] 17.3-40.5%) and 33.4% (95% CI 20.1-43.8%), respectively. Complete remission was achieved in 3%, marker-negative partial response (PR) in 41%, marker-positive PR in 18%, stable disease in 17% and progressive disease in 20%. In the second-line setting, the 2-year PFS rate was 43.5% (95% CI 21.7-60.8%) and 3-year OS 49.1% (95% CI 24.2-65.1%). In the third-line setting, the 2-year PFS rate was 21.0% (95% CI 9.5-35.4%) and the 3-year OS rate was 23.9% (95% CI 11.7-38.2). According to the current international prognostic factor study group criteria for first relapse for the high- and very high-risk group the 2-year PFS rates were 50% and 30%, respectively. There were two treatment-related deaths from IPO, and four from HDCT. Grade 3 or 4 toxicities included neutropenia (35%), thrombocytopaenia (18%), infection (15%), diarrhoea (11%) and lethargy (8%).
  
  
  CONCLUSIONS
  IPO offers an effective, well-tolerated, non-nephrotoxic alternative to cisplatin-based salvage regimens for patients with relapsed GCTs. It appears particularly useful in high-risk patients and for those in whom cisplatin is ineffective or contra-indicated.
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Waleed
authors.initials: W
authors.lastname: Badreldin
authors.affiliation: Charing Cross Hospital, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.affiliation: Guy's and St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: University College London Cancer Institute, London, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Harland
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Danish
authors.initials: D
authors.lastname: Mazhar
authors.affiliation: Charing Cross Hospital, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Harding
authors.affiliation: Charing Cross Hospital, London, UK.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Charing Cross Hospital, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Wilson
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Berney
authors.affiliation: Charing Cross Hospital, London, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shamash
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D018239:Seminoma / Q000188:drug therapy; D013736:Testicular Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin
keywords: cisplatin resistance; germ cell tumours; relapse