title: Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer.
  
  
  METHODS
  Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability.
  
  
  RESULTS
  PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms.
  
  
  CONCLUSIONS
  TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.
authors.affiliation: Paul A. DiSilvestro and Margaret M. Steinhoff, Women and Infants Hospital, Providence, RI; Shamshad Ali, Roswell Park Cancer Institute, Buffalo; Yi-Chun Lee, State University of New York Health Science Center, Brooklyn, NY; Peter S. Craighead, Tom Baker Cancer Center, Calgary, Alberta, Canada; Joseph A. Lucci, University of Miami School of Medicine, Miami, FL; David E. Cohn, Ohio State University, Columbus, OH; Nicola M. Spirtos, Women's Cancer Center of Nevada, Las Vegas, NV; Krishnasu S. Tewari, University of California Medical Center, Irvine, Orange, CA; Carolyn Muller, University of New Mexico Memorial Medical Center, Albuquerque, NM; Walter H. Gajewski, Zimmer Cancer Center, Wilmington, NC; and Bradley J. Monk, Creighton University School of Medicine, Phoenix, AZ.
authors.forename: Paul A
authors.initials: PA
authors.lastname: DiSilvestro
authors.forename: Shamshad
authors.initials: S
authors.lastname: Ali
authors.forename: Peter S
authors.initials: PS
authors.lastname: Craighead
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lucci
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Lee
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Spirtos
authors.forename: Krishnasu S
authors.initials: KS
authors.lastname: Tewari
authors.forename: Carolyn
authors.initials: C
authors.lastname: Muller
authors.forename: Walter H
authors.initials: WH
authors.lastname: Gajewski
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Steinhoff
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D018196:Carcinoma, Adenosquamous / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin