PLACEBO-CONTROLLED TRIAL OF SAFETY AND EFFICACY OF INTRAOPERATIVE CONTROLLED DELIVERY BY BIODEGRADABLE POLYMERS OF CHEMOTHERAPY FOR RECURRENT GLIOMAS

Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity . We have developed a method for local sustained release of chemothera peutic agents by their incorporation into biodegradable polymers. Impl antation of the drug-impregnated polymer at the tumour site allows pro longed local exposure with minimal systemic exposure. We conducted a r andomised, placebo-controlled, prospective study to evaluate the effec tiveness of biodegradable polymers impregnated with carmustine to trea t recurrent malignant gliomas. In 27 medical centres, 222 patients wit h recurrent malignant tumours requiring re-operation were randomly ass igned to receive surgically implanted biodegradable polymer discs with or without 3.85% carmustine. Randomisation balanced the treatment gro ups for all of the prognostic factors examined. Median survival of the 110 patients who received carmustine polymers was 31 weeks compared w ith 23 weeks for the 112 patients who received only placebo polymers ( hazard ratio=0.67, p=0006, after accounting for the effects of prognos tic factors). Among patients with glioblastoma, 6-month survival in th ose treated with carmustine-polymer discs was 50% greater than in thos e treated with placebo (mortality=32 of 72 [44%] vs 47 of 73 [64%], p= 0.02). There were no clinically important adverse reactions related to the carmustine polymer, either in the brain or systemically. Intersti tial chemotherapy delivered with polymers directly to brain tumours at the time of surgery seems to be a safe and effective treatment for re current malignant gliomas.