Accelerated radiotherapy, carbogen, and nicotinamide in glioblastoma multiforme: Report of European organization for research and treatment of cancertrial 22933

Purpose: A three-step phase I/II trial associating accelerated radiotherapy with carbogen (step 1, ARCO), with nicotinamide (step 2, ARN), or with bot h (step 3, ARCON) was conducted, the aim of which was to overcome the effec ts of proliferation and hypoxia as potential causes of tumor radioresistanc e in glioblastoma multiforme, Patients and Methods: Radiotherapy consisted of 60 Gy delivered over 4 week s in 1.5-Gy fractions twice daily, 5 days a week. Carbogen breathing was st arted 5 minutes before each fraction and continued until the end of each tr eatment session. Nicotinamide was given daily as a single oral dose of 85 m g/kg, Results: A total of 115 patients with a median age of 55 years were registe red. Of 107 eligible patients, 23 were registered in step 1, 28 in step 2, and 56 in step 3, The planned treatment was administered without any interr uption in 72% of patients (86% in ARCO but 68% in ARN and ARCON). The incid ence and severity of acute skin and mucous membrane toxicity were higher in patients who received nicotinamide (ie, the ARN and ARCON groups). Grade 1 to 2 gastrointestinal toxicity was observed in 44% of patients in the ARN group and 32% of patients in the ARCON group, but only in 8% of patients in the ARCO group. Eight percent of evaluated patients presented with abnorma l liver test results at treatment completion. The dose of corticosteroids h ad to be increased in 44% of patients. Late neurologic side effects were si milar in all treatment steps and were observed mostly in patients with dise ase progression. Median survival times for patients treated with ARCO, ARN, and ARCON were 10.1, 9.7, and 11.1 months, respectively. Conclusion: Feasibility of ARCO treatment was good but that of ARN and ARCO N was only fair. This probably reflected the higher acute toxicity rate, pa rticularly gastrointestinal, for patients receiving nicotinamide. The dose of corticosteroids had to be increased frequently during treatment, suggest ing a higher than expected acute neurologic toxicity. Overall survival was similar in the three treatment steps and not different when compared with r esults of of her series that used radiotherapy alone. (C) 1999 by American Society of Clinical Oncology.