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).
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.
Rischin
Danny
D
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
Peters
Lester
L
Fisher
Richard
R
Macann
Andrew
A
Denham
Jim
J
Poulsen
Michael
M
Jackson
Michael
M
Kenny
Lizbeth
L
Penniment
Michael
M
Corry
June
J
Lamb
David
D
McClure
Bev
B
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
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin; D005472:Fluorouracil