title: Topotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study.
abstract: OBJECTIVE
  Second-line treatment with paclitaxel and carboplatin enhances survival of women with platinum-sensitive recurrent ovarian cancer (ROC). However, because of its cumulative neurotoxicity, there is a strong demand for platinum-combinations with better therapeutic index. Because of its pharmacological properties, topotecan is a good adjunct to carboplatin in this setting, but its safety and efficacy remains to be defined.
  
  
  METHODS
  Patients with platinum-sensitive ROC were eligible in this multicenter phase I/II study, stratified according to treatment-free interval (TFI). Dose level 0 consisted of topotecan 1 mg/m(2)/d1-3/q21d plus carboplatin AUC5/d3/q21d. DLT was defined as grade > or =3 neutropenia or thrombocytopenia or grade > or =3 non-hematological toxicity excluding alopecia, nausea and vomiting, accompanied by a treatment delay >1 week.
  
  
  RESULTS
  From June 2004 to August 2005, 26 patients were enrolled, receiving a total of 145 cycles of chemotherapy. MTD was reached at topotecan 0.75 mg/m(2) and carboplatin AUC5. We observed a single grade 4 leucopenia. There were 3 (12%), 15 (58%) and 8 (31%) events of grade 3/4 hematological anaemia, leucopenia, and thrombocytopenia. Response rate was 67% (95% CI 43-85), median progression-free survival 9.5 months (95% CI 7.3-12.0), median overall survival 19.4 months (95% CI 12.3-26.9). None of the toxicity or efficacy endpoints were associated with TFI.
  
  
  CONCLUSIONS
  Topotecan and carboplatin is a well tolerated novel doublet option for women with platinum sensitive ROC. We encourage further studies on this approach, but to limit the doses of topotecan to 0.75 mg/m(2)/d1-3 and carboplatin AUC 5/d3.
authors.affiliation: Department of Obstetrics and Genecology, Charité University Hospital, Campus Virchow-Clinic, Berlin, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Koensgen
authors.forename: Dirk
authors.initials: D
authors.lastname: Stengel
authors.forename: Antje
authors.initials: A
authors.lastname: Belau
authors.forename: Peter
authors.initials: P
authors.lastname: Klare
authors.forename: Guelten
authors.initials: G
authors.lastname: Oskay-Oezcelik
authors.forename: Thomas
authors.initials: T
authors.lastname: Steck
authors.forename: Oumar
authors.initials: O
authors.lastname: Camara
authors.forename: Alexander
authors.initials: A
authors.lastname: Mustea
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Coumbos
authors.forename: Thomas
authors.initials: T
authors.lastname: Bogenrieder
authors.forename: Werner
authors.initials: W
authors.lastname: Lichtenegger
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019772:Topotecan; D016190:Carboplatin