title: Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR).
abstract: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC).
  
  
  
  Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points.
  
  
  
  A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia.
  
  
  
  The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.
authors: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité University Hospital of Berlin, Berlin, Germany jalid.sehouli@charite.de.
authors: J
authors: J
authors: Sehouli
authors: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité University Hospital of Berlin, Berlin, Germany.
authors: R
authors: R
authors: Chekerov
authors: Department of Gynecology and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria.
authors: A
authors: A
authors: Reinthaller
authors: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité University Hospital of Berlin, Berlin, Germany.
authors: R
authors: R
authors: Richter
authors: Department of Medical Oncology, MD Anderson Cancer Center Spain, Madrid, Spain.
authors: A
authors: A
authors: Gonzalez-Martin
authors: Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
authors: P
authors: P
authors: Harter
authors: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité University Hospital of Berlin, Berlin, Germany.
authors: H
authors: H
authors: Woopen
authors: Department of Obstetrics and Gynecology, Division of Gynecology, Medical University of Graz, Austria.
authors: E
authors: E
authors: Petru
authors: Department of Obstetrics and Gynaecology, Johann Wolfgang Goethe-University Frankfurt am Main.
authors: L C
authors: LC
authors: Hanker
authors: Department of Gynecology, Park Clinic Weißensee, Berlin.
authors: E
authors: E
authors: Keil
authors: Department of Gynecology and Obstetrics, Carl-Gustav Carus University, Dresden.
authors: P
authors: P
authors: Wimberger
authors: Gynecological Practice for Gynecologic Oncology and Women's Health, Berlin.
authors: P
authors: P
authors: Klare
authors: Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
authors: C
authors: C
authors: Kurzeder
authors: Department of Gynaecology and Obstetrics, University Hospital, Campus Kiel, Kiel.
authors: F
authors: F
authors: Hilpert
authors: Department of Gynaecology and Obstetrics, University Hospital Greifswald, Greifswald, Germany.
authors: A K
authors: AK
authors: Belau
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors: A
authors: A
authors: Zeimet
authors: Servicio de Oncología del Hospital Son Llazer de Palma de Mallorca, Mallorca, Spain.
authors: I
authors: I
authors: Bover-Barcelo
authors: Department of Gynecology and Obstetrics, Carl-Gustav Carus University, Dresden.
authors: U
authors: U
authors: Canzler
authors: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg.
authors: S
authors: S
authors: Mahner
authors: Department of Gynecology and Obstetrics, Evangelisches Krankenhaus, Duesseldorf, Germany.
authors: W
authors: W
authors: Meier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001317:Austria; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: ovarian cancer; platinum-sensitive; topotecan