title: Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR).
abstract: OBJECTIVE
  Effective therapies with a low rate of side effects are warranted in the 2nd-line setting in ovarian cancer. Both topotecan and the alkylating agent treosulfan have demonstrated efficacy in this patient group and are broadly used in Germany. Therefore, we started a prospectively randomized phase III trial comparing these two drugs in early recurrent ovarian cancer.
  
  
  METHODS
  Patients having relapsed after platinum-taxane therapy were randomized to receive either topotecan or treosulfan. Stratification depended on platinum sensitivity (stratum 1: up to 6 months after primary chemotherapy, stratum 2: 6 to 12 months).
  
  
  RESULTS
  A total of 274 patients were treated either with topotecan (136 patients) or treosulfan (138). Hematologic toxicity was significantly more frequent with topotecan but without severe clinical consequences. Non hematologic toxicity was similar in both study arms. Overall survival was significantly longer with topotecan (p=0.0023), with a median of 55.0 weeks versus 41.0 weeks as well as progression-free survival (p=0.0020) with a median of 23.1 weeks versus 12.7 weeks. Similar results were found for stratum 2 subgroup. Overall response rate was 27.5% for topotecan and 16.0% for treosulfan (p=0.0307). In stratum 1 progression-free survival was 18.1 weeks for topotecan and 9.4 weeks for treosulfan (p=0.0476), but there was no difference in overall survival in this prognostic poor subgroup.
  
  
  CONCLUSIONS
  This randomized phase III trial could detect superiority of topotecan versus treosulfan in patients with recurrent disease after platinum-paclitaxel combination therapy. Our experience indicates that optimization of systemic treatment could improve outcome even in this poor prognostic subgroup of patients with relapsed ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Evangelisches Krankenhaus, Duesseldorf, Germany. wmeier1620@aol.com
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Sigrid
authors.initials: S
authors.lastname: Olbricht
authors.forename: Martina
authors.initials: M
authors.lastname: Gropp
authors.forename: Barbara
authors.initials: B
authors.lastname: Richter
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lück
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Jacobus
authors.initials: J
authors.lastname: Pfisterer
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D015996:Survival Rate; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009944:Organoplatinum Compounds; D019772:Topotecan; C018404:treosulfan; D002066:Busulfan; D017239:Paclitaxel