title: Ifosfamide and vinorelbine in advanced platinum-resistant ovarian cancer: excessive toxicity with a potentially active regimen.
abstract: OBJECTIVE
  The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer.
  
  
  METHODS
  Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for the first 14 patients.
  
  
  RESULTS
  Between February 1997 and December 1998, 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed.
  
  
  CONCLUSIONS
  This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.
authors.affiliation: Medical Oncology Service, Alcala de Henares University, Madrid, 28034, Spain. agonzalez@hrc.insalud.es
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Martín
authors.forename: Carmen
authors.initials: C
authors.lastname: Crespo
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-López
authors.forename: Manuela
authors.initials: M
authors.lastname: Pedraza
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.forename: Enrique
authors.initials: E
authors.lastname: Lastra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Moyano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D009944:Organoplatinum Compounds; D014747:Vinblastine; D015080:Mesna; D017239:Paclitaxel; D000077235:Vinorelbine; D007069:Ifosfamide