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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)

From the Division of Haematology and Medical Oncology, Division of Radiation Oncology, and Statistical Centre, Peter MacCallum Cancer Centre, Melbourne; Department of Radiation Oncology, Newcastle Mater Hospital, Newcastle; Department of Radiation Oncology, QRI-Mater Hospital; Department of Radiation Oncology, QRI-Royal Brisbane Hospital, Brisbane; Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney; Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia; Department of Radiation Oncology, Auckland Hospital, Auckland; Department of Radiation Oncology, Wellington Hospital, Wellington, New Zealand

Address reprint requests to Danny Rischin, Division of Haematology and Medical Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Locked Bag No. 1, A’Beckett St, Melbourne 8006, Australia; e-mail: Danny.Rischin{at}petermac.org

PURPOSE: 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.

PATIENTS AND 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/m²) plus tirapazamine (290 mg/m²/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m²/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m²) on day 1 and infusional fluorouracil (360 mg/m²/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.

CONCLUSION: 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.

Supported by Sanofi-Synthelabo.

Presented at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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