title: Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer.
abstract: OBJECTIVE
  Reirradiation (re-RT) with concurrent chemotherapy offers a therapeutic option in patients who have locoregional recurrence of head and neck cancer (HNC). The hypoxic cell sensitizer, tirapazamine (TPZ), has demonstrated promising results in first-line therapy for HNC. This phase I trial was designed to test the feasibility of giving TPZ in the re-RT setting.
  
  
  METHODS
  Patients with recurrent HNC who received prior radiotherapy (RT) were enrolled and received TPZ (260 mg/m2) and cisplatin (50 mg/m2) Weeks 1, 3, and 5 concurrently with RT (72 Gy, 42 fractions over 6 weeks). TPZ (160 mg/m2) alone was added on Days 1, 3, and 5 of Week 2 (cohort 1) or Weeks 2 and 4 (cohort 2).
  
  
  RESULTS
  Twenty-five subjects were enrolled, 7 and 18 on cohorts 1 and 2, respectively. Significant toxicities included Grade 3 dermatitis (20%) and Grade 3 mucositis (40%). Dose-limiting toxicity was observed on cohort 2 (1 patient with aspiration pneumonia). Four deaths occurred during treatment. Two fatalities occurred after completing therapy as a result of carotid artery rupture. With a minimum and median follow-up of 14 and 24 months, respectively, median overall survival was 14 months with actuarial 1-year and 2-year survival of 56% and 27%, respectively.
  
  
  CONCLUSIONS
  Reirradiation with concomitant chemotherapy including TPZ in patients with unresectable recurrent HNC is feasible and results in long-term survival in a significant proportion of patients.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA. ecohen@medicine.bsd.uchicago.edu
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Dominique
authors.initials: D
authors.lastname: Rosine
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Elwyn
authors.initials: E
authors.lastname: Loh
authors.forename: Liji
authors.initials: L
authors.lastname: Shen
authors.forename: Antoine
authors.initials: A
authors.lastname: Lusinchi
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016001:Confidence Intervals; D005240:Feasibility Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage; D019233:Retreatment; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin