RADIOENDOCRINE THERAPY OF BRAIN-TUMORS WITH THE LONG-ACTING OPIOID ANTAGONIST NALTREXONE IN ASSOCIATION WITH RADIOTHERAPY

Aims and Background: Malignant gliomas remain untreatable as the different therapeutic combinations are generally only palliative. Recent experimental evidence suggests that endogenous opioid peptides are involved in brain tumor growth. The aim of the present study was to evaluate the effect on survival of concomitant administration of the long-acting opioid antagonist naltrexone (NTX) in patients with malignant astrocytomas treated with radiotherapy (RT). Methods: 21 patients with high grade malignant gliomas were randomized to receive RT alone or RT plus NTX. The dose of RT was 60 Gy. NTX was given orally at a dose of 100 mg every other day without interruption until disease progression. Results: The objective tumor regression rate in patients treated with RT plus NTX was higher than that of those treated with RT alone but not significantly so. On the contrary, the percentage of survivals at 1 year was significantly higher in patients treated with RT plus NTX than in those treated with RT alone (5/10 vs 1/11, P < 0.05). NTX therapy was substantially well tolerated in most patients. Conclusions: The finding of longer survival in brain tumor patients treated with RT plus NTX than in those who received RT alone suggests in vivo involvement of endogenous opioid peptides in regulating the growth of malignant astrocytomas.