TIRAPAZAMINE IS OUT

NEW YORK (Reuters Health) Jun 17 - Disappointing results in a phase III head-and-neck cancer trial: the hypoxic cytotoxin tirapazamine combined with cisplatin and radiation showed no overall survival advantage.

"The negative results of our trial were surprising based on previous experience with this regimen," lead researcher Dr. Danny Rischin told Reuters Health by e-mail. "Future trials of strategies targeting hypoxia will need to identify and select the subset of patients where hypoxia is limiting the effectiveness of current standard treatment."

Dr. Rischin of the University of Melbourne, Australia, and colleagues enrolled 861 patients with previously untreated stage III or IV squamous cell carcinoma at 89 sites in 16 countries.

As reported online May 17th in the Journal of Clinical Oncology, they randomly assigned patients to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with cisplatin alone or in combination with tirapazamine.

In intent-to-treat analysis, the 2-year overall survival rates were 65.7% for the cisplatin patients and 66.2% in the combination group. There were also no significant differences in failure-free survival, time to locoregional failure, or quality of life.

The study did yield some useful data. "A very important finding of our trial relates to the impact of poor quality radiotherapy on outcome in head and neck cancer," Dr. Rischin said. "Patients who had deficient radiotherapy plans had only a 50% 2-year survival rate, compared to 70% in the rest of the population."

"Centers treating small numbers of patients were the major source of problems," he added, which underlines "the importance of ensuring that head and neck cancer is treated in centers with appropriate expertise and ability to deliver high quality radiotherapy."

Abstract

J Clin Oncol 2010.