Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol

Purpose. Classical and new therapies in anaplastic astrocytomas and gliobla stomas do not yield sufficient results. Agents able to redifferentiate neop lastic cells in vitro are known. We proposed alfacalcidol, a vitamin D anal og able to bind to nuclear receptors regulating mitotic activity, in the tr eatment of malignant gliomas. Patients and methods. Patients with glioblastomas and anaplastic astrocytom as were enrolled in a phase II trial involving surgery or biopsy, radiother apy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol a t the daily dose of 0.04 mug/kg. MRI took place every 6 months. Results Eleven patients were included and completed the study. The series i nvolved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out o f 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the rad iological lesion, with a decrease of the gadolinium-enhanced area. Simultan eously, the patients showed a complete clinical remission, observed respect ively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas , 2 cases showed this response; after 4 years, 2 of 10 patients with gliobl astomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interrupt ion of the drug was necessary. Conclusions Alfacalcidol, an in vitro agent of redifferentiation, is safe a nd seems able to induce in some patients, in synergy with classical surgery -radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malig nant gliomas.