Phase II study of lonidamine plus radiotherapy in the treatment of brain metastases.

Twenty-nine patients received the cytotoxic radiosensitizing agent lonidamine before, during, and after cranial irradiation for brain metastases. One patient was ineligible (meningioma). In 28 eligible patients, median survival was 29 weeks (range, 2 to > 220 weeks). Nine patients (32%) survived > 1 year and 3 (11%) survived > 2 years. The major toxic effects of lonidamine were myalgias, nausea and vomiting, somnolence, and ototoxicity. There was no evidence that radiation skin toxicity or cerebral toxicity was increased by the addition of lonidamine. None of the patients experienced shrinkage of their extracerebral disease on lonidamine. Median survival duration in this study was at the upper limit of that reported in the literature for radiation alone, and the proportion of 2 year survivors was also higher than usual for radiation alone. Hence, further studies may be warranted.