title: Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study.
abstract: OBJECTIVE
  We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes.
  
  
  METHODS
  Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events.
  
  
  RESULTS
  The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680).
  
  
  CONCLUSIONS
  Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Case Western Reserve University and Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Shamshad
authors.initials: S
authors.lastname: Ali
authors.forename: Edwin
authors.initials: E
authors.lastname: Watkins
authors.forename: J Tate
authors.initials: JT
authors.lastname: Thigpen
authors.forename: Gunter
authors.initials: G
authors.lastname: Deppe
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Clarke-Pearson
authors.forename: Samuel
authors.initials: S
authors.lastname: Insalaco
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D006918:Hydroxyurea