Interstitial misonidazole. A preliminary report on a new perspective in clinical radiation sensitization and hypoxic cell chemotherapy.

The actions of misonidazole as a radiation sensitizer, hypoxic cytotoxic, and metabolic inhibitor are all concentration-dependent, and the commonly prescribed oral dose (12 g/m2) appears to be inadequate. The drug has, therefore, been given interstitially in solid form, when local tissue doses of the order of tens of millimolar are attained, to four patients, all with advanced disease. In the three cases (two squamous carcinomas and a malignant melanoma) in whom the drug concentration was considered to be adequate, a beneficial effect was obtained, which, in two instances, was associated with doses of radiation of 6 and 8 Gy, respectively. This approach has a wide potential application in cancer therapy.