Effect of High-Dose Tamoxifen on Malignant Gliomas

Oh, Yeon Chul; Kim, Jung Hoon; Lee, Jung Kyo; Kim, Chang Jin; Kwon, Yang; Rhim, Seung Chul; Kwun, Byung Duck; Whang, C Jin

Abstract

In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can suppress deoxyribonucleic acid(DNA) synthesis and cell proliferation in cultured human gliomas. This growth suppression is independent on its antiestrogenic properties. Tamoxifen may act through the inhibition of the enzyme protein kinase C(PKC), which transduces mitogenic signals from the cell surface to the nucleus. In order to evaluate the therapeutic response and side effect of high-dose tamoxifen, we performed a clinical study of 28 patients with malignant gliomas who were treated with high-dose tamoxifen in our hospital between February 1991 and January 1993. An effect was defined as a statistically improved survival times/rates. In patients who were assigned to receive high-dose tamoxifen, it was first administered at standard antiestrogen doses(20mg orally bid/day) to observe for any side effect and if tolerated, the dose was increased weekly to achieve target doses(100mg orally bid/day) over a 1 month period. We compared the survival times/rates between anaplastic astrocytomas and glioblastoma mutiformes. Although the median survival time was slightly longer in anaplastic astrocytomas than that of glioblastoma multiformes, there was no statistical difference of survival curves between two groups at the p=0.05 level. We also examined the survival times/rates of malignant gliomas according to treatment modalities(radiotherapy alone, radiotherapy plus ACNU, and radiotherapy plus tamoxifen). Although the survival rate and time were slightly higher in radiotherapy plus tamoxifen group than those of another treatment groups, we could not find the statistical significance of survival curves between three treatment groups(p>0.05). High-dose oral tamoxifen appeared to be well tolerated in most patients. Five patients developed anorexia following dose escalation of tamoxifen. Another complications were amenorrhea, nausea/vomiting, and constipation. There were no changes in hematological studies that could be attributed to tamoxifen. We think that high-dose tamoxifen cah be administered safely to malignant gliomas patients. Our results were not impressive. We conclude that the definition of the true efficacy of high-dose tamoxifen in patients harboring malignant gliomas is not possible from this limited study, and a further large scale, randomized trial of this agent is necessary.