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

Aleck A Hercbergs; Lav K Goyal; John H Suh; Sy Lee; Chandana A Reddy; Bruce H Cohen; Glen H Stevens; Sethu K Reddy; David M Peereboom; Paul J Elson; Manjula K Gupta; Gene H Barnett

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

Anticancer Res. 2003 Jan-Feb;23(1B):617-26.

Authors

Aleck A Hercbergs¹, Lav K Goyal, John H Suh, Sy Lee, Chandana A Reddy, Bruce H Cohen, Glen H Stevens, Sethu K Reddy, David M Peereboom, Paul J Elson, Manjula K Gupta, Gene H Barnett

Affiliation

¹ Department of Radiation Oncology, Cleveland Clinic Foundation, 9500 Euclid Ave, S80, Cleveland, OH 44195, USA.

PMID: 12680157

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.

Publication types

Clinical Trial
Clinical Trial, Phase I
Clinical Trial, Phase II

MeSH terms

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

Substances

Antineoplastic Agents, Hormonal
Antithyroid Agents
Tamoxifen
Insulin-Like Growth Factor I
Propylthiouracil
Thyrotropin