title: Concurrent tirapazamine and radiotherapy for advanced head and neck carcinomas: a Phase II study.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of tirapazamine, a hypoxic cytotoxin, combined with conventional radiotherapy (RT) for advanced head and neck carcinomas.
  
  
  METHODS
  From Oct. 1994 to Nov. 1996, 40 patients with stage III or IV carcinomas of the head and neck were enrolled in a Phase II trial to receive conventional RT (70 Gy in 7 weeks) with concurrent tirapazamine (159 mg/m2 intravenously, 3 times per week for 12 doses). One patient subsequently withdrew from the protocol treatment, and was excluded from analyses. Among the 39 cases, the primary sites were located in the oropharynx (n = 28), supraglottic larynx (n = 6), or hypopharynx (n = 5). Twenty-seven patients had T3 or T4, and 27 had N2 or N3 disease.
  
  
  RESULTS
  Thirty-two (82%) patients received full 12 drug doses. Thirty-two patients (82%) received full 70 Gy of RT. The most frequent drug toxicities were muscle cramps (77%) and nausea/vomiting (62%), usually grade 1 or 2. Overall, 13 patients (33%) experienced grade 3 or 4 drug-related toxicities. No excessive RT-associated acute normal tissue reactions were observed. With a median follow-up of 13 months, the 1-year and 2-year local control rate was 64% and 59% respectively.
  
  
  CONCLUSIONS
  The tirapazamine regimen was well tolerated with a compliance rate of 82%. The toxicity of RT with concurrent tirapazamine was acceptable in treating advanced head and neck carcinomas. The disease control trend was encouraging. Further clinical studies are warranted.
authors.affiliation: Johns Hopkins Hospital, Baltimore, MD 21287-8922, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Trotti
authors.forename: S
authors.initials: S
authors.lastname: Spencer
authors.forename: R
authors.initials: R
authors.lastname: Rostock
authors.forename: C
authors.initials: C
authors.lastname: Fisher
authors.forename: R
authors.initials: R
authors.lastname: von Roemeling
authors.forename: E
authors.initials: E
authors.lastname: Harvey
authors.forename: E
authors.initials: E
authors.lastname: Groves
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D000077704:Tirapazamine; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine