title: Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.
abstract: OBJECTIVE
  To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.
  
  
  METHODS
  Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).
  
  
  RESULTS
  Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.
  
  
  CONCLUSIONS
  Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.
authors: National Cancer Institute/Institute of Biomedical Research, Universidad Nacional Autónoma de México, México City, México.
authors: Alfonso
authors: A
authors: Dueñas-González
authors: Juan J
authors: JJ
authors: Zarbá
authors: Firuza
authors: F
authors: Patel
authors: Juan C
authors: JC
authors: Alcedo
authors: Semir
authors: S
authors: Beslija
authors: Luis
authors: L
authors: Casanova
authors: Pittayapoom
authors: P
authors: Pattaranutaporn
authors: Shahid
authors: S
authors: Hameed
authors: Julie M
authors: JM
authors: Blair
authors: Helen
authors: H
authors: Barraclough
authors: Mauro
authors: M
authors: Orlando
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine