title: A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).
abstract: OBJECTIVE
  In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC.
  
  
  METHODS
  Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2d1 q4w or treosulfan p.o. 600 mg/m2d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life.
  
  
  RESULTS
  250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred.
  
  
  CONCLUSIONS
  Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.
authors.affiliation: Gynecology and Gynecologic Oncology, Charité University Medicine Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany. jalid.sehouli@charite.de.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Gynecologic Cancer Centre Karlsruhe, St. Vincentius Clinics, Karlsruhe, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tomè
authors.affiliation: Gynecology and Gynecologic Oncology, Charité University Medicine Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Desislava
authors.initials: D
authors.lastname: Dimitrova
authors.affiliation: Centre for Gynecology, Hufeland Clinic, Bad Langensalza, Germany.
authors.forename: Oumar
authors.initials: O
authors.lastname: Camara
authors.affiliation: Clinic for Gynecology and Obstetrics, University Clinic, Jena, Germany.
authors.forename: Ingo Bernhard
authors.initials: IB
authors.lastname: Runnebaum
authors.affiliation: Oncology Practise, Goslar, Germany.
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Tessen
authors.affiliation: Gynecology and Gynecologic Oncology, University Clinic, Freiburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Rautenberg
authors.affiliation: Gynecology and Gynecologic Oncology, Charité University Medicine Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Chekerov
authors.affiliation: Gynecology and Gynecologic Oncology, Charité University Medicine Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Mustafa Zelal
authors.initials: MZ
authors.lastname: Muallem
authors.affiliation: Department of OOGYN, Gyncecological University Cancer Center of Franconia, University Hospital Erlangen, CCC Erlangen-EMN, Erlangen, Germany.
authors.forename: Michael Patrick
authors.initials: MP
authors.lastname: Lux
authors.affiliation: iOMEDICO Clinical Research, Freiburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Trarbach
authors.affiliation: Gynecology and Gynecologic Oncology, University Clinic, Freiburg, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gitsch
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: C018404:treosulfan; D002066:Busulfan
keywords: Oral versus intravenous; Ovarian cancer; Recurrent; Treosulfan