Malignant glioma sensitivity to radiotherapy, high-dose tamoxifen, and hypericin: corroborating clinical response in vitro: case report.

ABSTRACT

Previous work has demonstrated the importance of protein kinase C in regulating glioma cell proliferation in vitro. Tamoxifen, a protein kinase C inhibitor when administered in high dosages, is currently being used as an adjuvant in the treatment of patients with malignant gliomas. The patient in the present study harbored a left frontal anaplastic astrocytoma adjacent to Broca's area and the paracentral region, which limited gross resection. After a subtotal resection of the tumor and after radiation, the patient was administered high-dose tamoxifen therapy for gross residual gadolinium-enhancing regions that were revealed by magnetic resonance imaging and by high glucose uptake as demonstrated by positron emission tomography. After treatment, a decrease in gadolinium enhancement on magnetic resonance images and a decrease in glucose uptake revealed by positron emission tomography were noted. A laboratory examination of the tissue obtained from the original surgical resection revealed resistance to radiation therapy but sensitivity to tamoxifen as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay. The subsequent in vitro testing of the tumor that was removed after the recurrence of tumor (22 months after the initiation of tamoxifen) revealed loss of sensitivity to tamoxifen. However, the recurrent tumor remained sensitive to growth inhibition by the potent protein kinase C inhibitor, hypericin, despite loss of sensitivity to tamoxifen in vitro, suggesting the potential clinical application of this agent. This close in vitro correlation with the clinical course of the patient in the present study suggests a potential role for such in vitro radiation and chemosensitivity testing in designing a rational individualized clinical course of treatment.