Clinical Experience with Intravenous Misonidazole for Carcinoma of the Esophagus: Results in Attempting Radiosensitization of Each Fraction of Exposure

Abstract

By using intravenous misonidazole, a hypoxic cell radiosensitizer, we attempted to test the hypothesis of hypoxia as the basis of the relatively poor results seen with radiation therapy in the treatment of carcinoma of the thoracic esophagus. As the peripheral neuropathy of misonidazole was well recognized, we felt that an adequate dose of misonidazole could be given approximately ten times before peripheral neuropathy would necessitate its discontinuation. Because of a desire to maximize any possible effects of radiosensitization, it was decided to administer misonidazole with each fraction of radiation, attempting to deliver curative radiation therapy with only ten fractions of radiation. We thus devised a scheme of radiation consisting of 400 rad twice a week for 5 weeks, a total of 4000 rad. Originally the attempt was made to utilize preoperative radiation therapy and assess the histologic specimens for efficacy. However, major pulmonary toxicity caused revision of that plan. Twenty six patients were treated with radiotherapy alone without surgery, 12 of the patients being randomized to receive intravenous misonidazole with 10 fractions of 400 rad each. In terms of partial response, complete response, local control, and long-term survival, there was no suggestion of any benefit of intravenous misonidazole in these patients. As a consequence, although the number of study patients was small, the investigation was discontinued. Possible explanations for the failure to demonstrate any benefit of misonidazole are discussed.