title: Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology.
abstract: The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer.
  
  
  
  Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally.
  
  
  
  Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%.
  
  
  
  Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.
authors.affiliation: *Department of Gynecology and Obstetrics, University Medicine Greifswald, Greifswald; †Department of Gynecology and Gynecological Oncology, Charité Berlin, Berlin; ‡Department of Urology, University Medicine Greifswald, Greifswald; §Department of Obstetrics and Gynecology, University Hospital Heidelberg; and ∥Department of Obstetrics and Gynecology, Städtisches Klinikum Brandenburg, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Koensgen
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Antje
authors.initials: A
authors.lastname: Belau
authors.forename: Martin
authors.initials: M
authors.lastname: Weiss
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
authors.forename: Vivien
authors.initials: V
authors.lastname: Grokopf
authors.forename: Michael
authors.initials: M
authors.lastname: Eichbaum
authors.forename: Peter
authors.initials: P
authors.lastname: Ledwon
authors.forename: Werner
authors.initials: W
authors.lastname: Lichtenegger
authors.forename: Marek
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Günter
authors.initials: G
authors.lastname: Köhler
authors.forename: Alexander
authors.initials: A
authors.lastname: Mustea
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*
chemical_list: D016190:Carboplatin; D015080:Mesna; D007069:Ifosfamide