title: Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).
abstract: OBJECTIVE
  To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial.
  
  
  METHODS
  One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost).
  
  
  RESULTS
  Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms.
  
  
  CONCLUSIONS
  Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.
authors.affiliation: Division of Haematology and Medical Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Locked Bag No. 1, A'Beckett St, Melbourne 8006, Australia. Danny.Rischin@petermac.org
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Lester
authors.initials: L
authors.lastname: Peters
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.forename: Andrew
authors.initials: A
authors.lastname: Macann
authors.forename: Jim
authors.initials: J
authors.lastname: Denham
authors.forename: Michael
authors.initials: M
authors.lastname: Poulsen
authors.forename: Michael
authors.initials: M
authors.lastname: Jackson
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Kenny
authors.forename: Michael
authors.initials: M
authors.lastname: Penniment
authors.forename: June
authors.initials: J
authors.lastname: Corry
authors.forename: David
authors.initials: D
authors.lastname: Lamb
authors.forename: Bev
authors.initials: B
authors.lastname: McClure
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin; D005472:Fluorouracil