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      Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study.

      Anticancer research

      Adult, Aged, Antineoplastic Agents, Hormonal, adverse effects, therapeutic use, Antithyroid Agents, Astrocytoma, drug therapy, Brain Neoplasms, blood, metabolism, Dose-Response Relationship, Drug, Female, Glioblastoma, Glioma, Humans, Hypothyroidism, chemically induced, Insulin-Like Growth Factor I, Male, Middle Aged, Neoplasm Recurrence, Local, Oligodendroglioma, Propylthiouracil, Tamoxifen, Thyroid Gland, drug effects, Thyrotropin

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          Abstract

          High-dose tamoxifen has had disappointing results as a palliative therapy in recurrent glioma. Insulin-like growth factor 1 (IGF-1) is a thyroid hormone modulated naturally occurring antagonist of tamoxifen-induced cytotoxicity. Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma. Tamoxifen was started within one month and given in escalating doses from 40 mg twice a day up to 80 mg 3 times a day. No significant toxicity developed. Eleven out of 22 patients became hypothyroid. No patients experienced symptoms of clinical hypothyroidism. Median survival was significantly longer in the hypothyroid group (10.1 months versus 3.1 months); p = 0.03. There was a significant decrease in blood levels of IGF-1 (p = 0.02). in hypothyroid patients. Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.

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          12680157

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