title: Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group.
abstract: OBJECTIVE
  The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.
  
  
  METHODS
  Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m(2)/d, topotecan 1.0 mg/m(2) plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2) on day 1 and 600 mg/m(2) on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).
  
  
  RESULTS
  The trial enrolled 502 patients with a mean age of 60.5 years (+/- 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.
  
  
  CONCLUSIONS
  Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.
authors.affiliation: Department of Gynecology,Charité University Medical Center, Berlin, Germany. sehouli@aol.com
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Dirk
authors.initials: D
authors.lastname: Stengel
authors.forename: Guelten
authors.initials: G
authors.lastname: Oskay-Oezcelik
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Peter
authors.initials: P
authors.lastname: Klare
authors.forename: Martina
authors.initials: M
authors.lastname: Stauch
authors.forename: Axel
authors.initials: A
authors.lastname: Paulenz
authors.forename: Oumar
authors.initials: O
authors.lastname: Camara
authors.forename: Elke
authors.initials: E
authors.lastname: Keil
authors.forename: Werner
authors.initials: W
authors.lastname: Lichtenegger
mesh_terms: D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016016:Proportional Hazards Models; D011788:Quality of Life; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005047:Etoposide; D019772:Topotecan; D000093542:Gemcitabine