TREATMENT OF RECURRENT MALIGNANT GLIOMAS WITH CHRONIC ORAL HIGH-DOSE TAMOXIFEN

The present clinical trial was undertaken to assess the clinical safet y and possible efficacy of administering tamoxifen to patients with re current malignant glial tumors at dosages calculated to achieve levels sufficient to inhibit protein kinase C within the tumor cells, Chroni c p.o. tamoxifen was administered in very high dosages to 32 patients (20 males and 12 females; age range, 26-75 years; mean, 49 years) with histologically verified malignant glioma [anaplastic astrocytoma (12 patients) or glioblastoma multiforme (20 patients)] who had demonstrat ed clinical and radiographical progression or recurrence following ext ernal beam radiation therapy (and additional chemotherapy in 11; immun otherapy in 2), The dosage of tamoxifen administered was 200 mg/day to males and 160 mg/day to females given in a twice daily schedule, Clin ical and radiographical (defined as a greater than 50% decrease in vol ume of the enhancing lesion volume on magnetic resonance imaging and a decrease in metabolic activity on serial positron emission tomographi c scans) response was noted in 8 patients (25%; 4/12 with anaplastic a strocytoma and 4/20 glioblastoma multiforme), with an additional 6 pat ients (19%) exhibiting stabilization of disease with minimal side effe cts, Median survival from the time of diagnosis for the entire cohort was 24 months (104 weeks), for the anaplastic astrocytoma group 42.5 m onths (185 weeks), and for the glioblastoma group 17.4 months (75.5 we eks), From the initiation of tamoxifen, median survival for the entire cohort was 10.1 months (44 weeks), for the anaplastic astrocytoma gro up 16 months (69 weeks), and for the glioblastoma group 7.2 months (31 weeks), The mean length of follow-up of all patients after initiating tamoxifen was 16 months (69 weeks), while the mean length of follow-u p of alive patients is 22.6 months (98 weeks) (range up to 51 months), These data suggest that a subgroup of patients with malignant gliomas respond or stabilize with chronic high-dose tamoxifen therapy, This t herapy may represent an alternative or adjuvant to existing chemothera pies for these tumors; further clinical trials are warranted.