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


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.


CONCLUSIONS
Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.
Hercbergs
Aleck A
AA
Department of Radiation Oncology, Cleveland Clinic Foundation, 9500 Euclid Ave, S80, Cleveland, OH 44195, USA.
Goyal
Lav K
LK
Suh
John H
JH
Lee
Sy
S
Reddy
Chandana A
CA
Cohen
Bruce H
BH
Stevens
Glen H
GH
Reddy
Sethu K
SK
Peereboom
David M
DM
Elson
Paul J
PJ
Gupta
Manjula K
MK
Barnett
Gene H
GH
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D009837:Oligodendroglioma / Q000188:drug therapy; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use*; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D013956:Antithyroid Agents; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D011441:Propylthiouracil; D013972:Thyrotropin