A study of the effect of misonidazole in conjunction with radiotherapy for the treatment of head and neck cancer. MRC working party on misonidazole in head and neck cancer

Abstract

The effect of the hypoxic cell sensitiser misonidazole as an adjuvant to radiotherapy of head and neck cancer was tested in a randomised double blind study. Patients with squamous carcinoma of the upper alimentary and respiratory tract, excluding those with early disease for which the prognosis was good, who were deemed suitable for radical radiotherapy and fit to receive the drug were entered into the study. Two radiotherapy regimes were employed, 10 fractions in 3 weeks to a modal tumour dose of 4000-4500 cGy, and 20 fractions in 4 weeks to a modal tumour dose of 5000-5750 cGy. Participating radiotherapists opted for one of the two schemes. Misonidazole or placebo capsules were administered 4 to 5 hours before each fraction of radiotherapy to a total of 11 to 13 g/m2. 168 patients were treated with 10 fractions and 99 with 20 fractions, between March 1979 and November 1981, when entry was stopped because of the high incidence of drug toxicity and lack of benefit. The estimated hazard ratio for local control was 0.89, indicating a slight advantage to misonidazole which was not statistically significant (p = 0.5). Peripheral neuropathy occurred in 56 patients who received misonidazole, and was more severe when treatment was given in 10 fractions.