Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group.
OBJECTIVE
Promising results in a randomized phase II trial with the hypoxic cytotoxin tirapazamine (TPZ) combined with cisplatin (CIS) and radiation led to this phase III trial.


METHODS
Patients with previously untreated stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either CIS (100 mg/m(2)) on day 1 of weeks 1, 4, and 7 or CIS (75 mg/m(2)) plus TPZ (290 mg/m(2)/d) on day 1 of weeks 1, 4, and 7 and TPZ alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS). The primary end point was overall survival (OS). The planned sample size was 850, estimated to result in 334 deaths, which would provide 90% power to detect a difference in 2-year survival rates of 60% v 70% for CIS versus TPZ/CIS, respectively (hazard ratio = 0.69).


RESULTS
Eight hundred sixty-one patients were accrued from 89 sites in 16 countries. In an intent-to-treat analysis, the 2-year OS rates were 65.7% for CIS and 66.2% for TPZ/CIS (TPZ/CIS--CIS: 95% CI, -5.9% to 6.9%). There were no significant differences in failure-free survival, time to locoregional failure, or quality of life as measured by Functional Assessment of Cancer Therapy-Head and Neck.


CONCLUSIONS
We found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves OS.
Rischin
Danny
D
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Danny.Rischin@petermac.org
Peters
Lester J
LJ
O'Sullivan
Brian
B
Giralt
Jordi
J
Fisher
Richard
R
Yuen
Kally
K
Trotti
Andy
A
Bernier
Jacques
J
Bourhis
Jean
J
Ringash
Jolie
J
Henke
Michael
M
Kenny
Lizbeth
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D011788:Quality of Life; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin