title: A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study.
abstract: BACKGROUND
  Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity.
  
  
  METHODS
  An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS).
  
  
  RESULTS
  Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001).
  
  
  CONCLUSIONS
  Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.
authors.affiliation: Department of Gynecology, European Competence Centre for Ovarian Cancer, Charité-University Hospital, Berlin. Electronic address: sehouli@aol.com.
authors.forename: J
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Department of Gynecology, Jena University Hospital, Jena.
authors.forename: I B
authors.initials: IB
authors.lastname: Runnebaum
authors.affiliation: Department of Gynecology, European Competence Centre for Ovarian Cancer, Charité-University Hospital, Berlin.
authors.forename: C
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: Brustzentrum, Sankt-Gertrauden-Krankenhaus, Berlin.
authors.forename: U
authors.initials: U
authors.lastname: Blohmer
authors.affiliation: Department of Gynecology, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald.
authors.forename: A
authors.initials: A
authors.lastname: Belau
authors.affiliation: Klinik fuer Strahlentherapie, Bruederkrankenhaus St Josef, Paderborn.
authors.forename: H
authors.initials: H
authors.lastname: Leber
authors.affiliation: Department of Obstetrics and Gynecology, J.W. Goethe-University, Frankfurt.
authors.forename: L C
authors.initials: LC
authors.lastname: Hanker
authors.affiliation: Department of Gynecology, Klinikum Frankfurt (Oder) GmbH, Frankfurt-Oder.
authors.forename: W
authors.initials: W
authors.lastname: Hartmann
authors.affiliation: Department of Gynecology, European Competence Centre for Ovarian Cancer, Charité-University Hospital, Berlin.
authors.forename: R
authors.initials: R
authors.lastname: Richter
authors.affiliation: Department of Gynecology, Universitätsklinikum Bonn, Bonn.
authors.forename: M D
authors.initials: MD
authors.lastname: Keyver-Paik
authors.affiliation: Department of Gynecology, Kath. Kliniken Essen-Nord Marienhospital, Altenessen.
authors.forename: C
authors.initials: C
authors.lastname: Oberhoff
authors.affiliation: Gyn-oncological Praxis, Fürstenwalde.
authors.forename: G
authors.initials: G
authors.lastname: Heinrich
authors.affiliation: Department of Gynecology, Horst Schmidt Klinik, Wiesbaden.
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.affiliation: Department of Gynecology, DRK Kliniken Berlin Westend, Berlin.
authors.forename: C
authors.initials: C
authors.lastname: Olbrich
authors.affiliation: Department of Gynecology, Kreiskrankenhaus Torgau Johann Kentmann GmbH, Torgau.
authors.forename: E
authors.initials: E
authors.lastname: Simon
authors.affiliation: Department of Gynecology, Universitätsklinik LMU, Munich.
authors.forename: K
authors.initials: K
authors.lastname: Friese
authors.affiliation: Department of Gynecology, Universitätsklinikum Essen, Essen.
authors.forename: R
authors.initials: R
authors.lastname: Kimmig
authors.affiliation: Department of Radiation Oncology, Charite-University Medicine Berlin, Campus Virchow-Klinikum, Berlin.
authors.forename: D
authors.initials: D
authors.lastname: Boehmer
authors.affiliation: Department of Gynecology, European Competence Centre for Ovarian Cancer, Charité-University Hospital, Berlin.
authors.forename: W
authors.initials: W
authors.lastname: Lichtenegger
authors.affiliation: Brustzentrum, Kliniken Essen-Mitte, Essen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kuemmel
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018196:Carcinoma, Adenosquamous / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000628:therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin