Radiotherapy with tirapazamine and cisplatin has "promising efficacy" for locally advanced head and neck cancer

Outcomes in locoregionally advanced head and neck cancer are improved by adding concurrent platinum-based chemotherapy to radiation, but the optimal chemotherapy dose and schedule is unclear. This Trans Tasman Radiation Oncology Group (TROG) randomised phase II trial investigated two chemoradiotherapy strategies for patients with previously untreated stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx. All patients were given 70Gy radiation therapy in 35 fractions for 7 weeks. Arm 1 (TPZ/CIS) with 63 patients included tirapazamine, which is preferentially cytotoxic to hypoxic cells and has been shown in preclinical studies to potentiate radiation and cisplatin cytotoxicity. Cisplatin (75 mg/m2) was given before radiotherapy in weeks 1,4 and 7. The second chemoboost arm included 58 patients given cisplatin (50 mg/m2) and fluorouracil in weeks 6 and 7. The complete response rate at 26 weeks was 71% in the TPZ/CIS arm and 66% in the chemoboost arm and the incidence of motor regional failure at two years was 14% compared to 30%. The three-year failure free survival rates were 55% and 44%, three-year locoregional failure free rate was 84% and 66% and three-year overall survival was 60% and 46% respectively. These were not statistically significantly different but differences in locoregional control became statistically significant after adjustment for known prognostic factors and failure free survival became of borderline significance.Toxicity data showed that the duration of acute mucositis was similar between groups but the median duration of greater than grade 2 skin reaction was 21 days in the TPZ/CIS and 35 days in the chemoboost group. Grade III and IV neutropenia occurred in 37% compared to 17% of patients and associated infection occurred in 23% compared to 7.4% in the chemoboost arm. The incidence of nausea, cramping, skin rash, fatigue and decline in performance status was significantly greater in the TPZ/CIS group.The authors concluded that based on the results of this trial, a phase III trial comparing TPZ/CIS to conventional fractionated radiotherapy with cisplatin is accruing patients to assess the efficacy of tirapazamine added to chemoradiotherapy in patients with locally advanced head and neck cancer.Reference...