PROGRESS REPORT OF A PHASE-II AND A PHASE-III TRIAL WITH ETANIDAZOLE (SR-2508) - A MULTICENTER EUROPEAN STUDY

A group of 6 European cancer centers, coordinated by the Institut Gustave-Roussy, began a phase II trial of the radiosensitizing drug, etanidazole, in November 1986. The trial was designed to study the toxicity of the drug and the feasibility of a phase III trial on the combination of etanidazole with radiotherapy for treating head and neck squamous cell carcinomas. Thirty-one patients were included in the phase II trial between November 1986 and June 1987; 25 completed the whole course of treatment. Most of the neuropathies occurred during the two weeks following radiotherapy, but had no major effect on radiotherapy itself. The area under the curve (AUC) was measured in 22 patients; there was no correlation between total AUC and the incidence of neuropathy, although there was a trend towards more neuropathies at high total AUC. The toxicity of Eta did not appear excessive. A phase III trial was therefore begun in July 1987. Twenty-nine centers in 5 European countries (France, Italy, Germany, Austria and the UK) took part. A total of 330 patients had been enrolled by the end of November 1989. This report presents the results available to date. 15% of the patients treated with Eta plus radiotherapy have received less than 15 Eta injections mainly because of skin rashes (5%), peripheral neuropathies (3%) or patient refusal (3%). The overall frequency of neuropathies was 27%, but most were grade I and occur mainly after treatment. There were similar percentages of radiotherapy-related toxicities, mainly acute reactions in irradiated normal tissues, in both Eta and control arms. Patients are being recruited to the study at about 12 patients per month, indicating that the target, 400 cases, will be reached by the end of April 1990. A preliminary analysis of the therapeutic efficacy of Eta in the radiotherapy of head and neck squamous cell carcinomas should be available by mid 1991.