Thema: News: Tamoxifen in Recurrent High Grade Glioma
News: Tamoxifen in Recurrent High Grade Glioma
Tom[a]
26.05.2002 17:39:36
AACR: Chemical Hypothyroidism Improves Survival and Response to Tamoxifen in Recurrent High Grade Glioma
By Peggy Peck
Special to DG News
SAN FRANCISCO, CA -- March 9, 2002 -- Propylthiouracil-induced chemical hypothyroidism combined with high dose tamoxifen more than doubled survival in a small study of recurrent high-grade glioma, according to findings reported here yesterday at the 93rd Annual Meeting of the American Association for Cancer Research.
In the study of 34 patients with recurrent glioma who became hypothyroid survived for an average of 11 months, compared to an average four-month survival for patients who did not become hypothyroid, said Dr. Aleck Hercbergs, a radiation oncologist at the Cleveland Clinic Foundation, Cleveland, Ohio.
Dr. Hercbergs said the "thyroid is a potent regulator of cell growth." Other researchers have observed that low thyroid function is sometimes associated with "better outcomes in some cancers".
In vitro studies suggested that the insulin-like growth factor-1 (IGF-1) is mitogenic and anti-apoptotic in glioma cell cultures and inhibits tamoxifen-induced cytotoxicity, suggesting a downregulation of IGF-1 in RG patients might improve response to tamoxifen.
In all 34 patients, hypothyroidism was induced with propylthiouracil 600-1000 mg/day and Lugol´s solution 30 mg tid for 14 days; 28 patients were also treated with 240 mg/day of tamoxifen. Tamoxifen at 240 mg/day was initiated within 30 days of study entry in the first 22 patients. In seven of the remaining 12 patients, tamoxifen was initiated only when chemically induced hypothyroidism was achieved.
Eighteen patients achieved chemical hypothyroidism; and 28 percent of these had more than 50 percent reduction in bi-dimensional size of the tumor on magnetic resonance imaging. None of the patients who remained euthyroid experienced tumor reduction.
Dr. Hercbergs was unable to explain why some patients failed to achieve hypothyroidism but said "younger patients tended to be more responsive to thyroid manipulation."
Dr. Daniel Karp, deputy director of cancer medicine at University of Texas-MD Anderson Cancer Center, in Houston, Texas, said Dr. Hercbergs´ study results are encouraging but added it is too soon to suggest that cancer specialists should induce "hypothyroidism in cancer patients."
Dr. Karp pointed out that hypothyroidism has "its own burden of disease. It causes exhaustion and depression, for example." Hypothyroidism is a common side effect of chemotherapy and standard of care is to administer thyroid hormone to "return the patient to a euthyroid state. I think this is still the desirable approach," he said.
Nonetheless, Dr. Hercbergs said, "having established the principle that lower thyroid function is favorable, it seems counter-productive to restore normal function while giving chemotherapy. It is like stepping on the brake, when you have the accelerator pressed to the floor."
By Peggy Peck
Special to DG News
SAN FRANCISCO, CA -- March 9, 2002 -- Propylthiouracil-induced chemical hypothyroidism combined with high dose tamoxifen more than doubled survival in a small study of recurrent high-grade glioma, according to findings reported here yesterday at the 93rd Annual Meeting of the American Association for Cancer Research.
In the study of 34 patients with recurrent glioma who became hypothyroid survived for an average of 11 months, compared to an average four-month survival for patients who did not become hypothyroid, said Dr. Aleck Hercbergs, a radiation oncologist at the Cleveland Clinic Foundation, Cleveland, Ohio.
Dr. Hercbergs said the "thyroid is a potent regulator of cell growth." Other researchers have observed that low thyroid function is sometimes associated with "better outcomes in some cancers".
In vitro studies suggested that the insulin-like growth factor-1 (IGF-1) is mitogenic and anti-apoptotic in glioma cell cultures and inhibits tamoxifen-induced cytotoxicity, suggesting a downregulation of IGF-1 in RG patients might improve response to tamoxifen.
In all 34 patients, hypothyroidism was induced with propylthiouracil 600-1000 mg/day and Lugol´s solution 30 mg tid for 14 days; 28 patients were also treated with 240 mg/day of tamoxifen. Tamoxifen at 240 mg/day was initiated within 30 days of study entry in the first 22 patients. In seven of the remaining 12 patients, tamoxifen was initiated only when chemically induced hypothyroidism was achieved.
Eighteen patients achieved chemical hypothyroidism; and 28 percent of these had more than 50 percent reduction in bi-dimensional size of the tumor on magnetic resonance imaging. None of the patients who remained euthyroid experienced tumor reduction.
Dr. Hercbergs was unable to explain why some patients failed to achieve hypothyroidism but said "younger patients tended to be more responsive to thyroid manipulation."
Dr. Daniel Karp, deputy director of cancer medicine at University of Texas-MD Anderson Cancer Center, in Houston, Texas, said Dr. Hercbergs´ study results are encouraging but added it is too soon to suggest that cancer specialists should induce "hypothyroidism in cancer patients."
Dr. Karp pointed out that hypothyroidism has "its own burden of disease. It causes exhaustion and depression, for example." Hypothyroidism is a common side effect of chemotherapy and standard of care is to administer thyroid hormone to "return the patient to a euthyroid state. I think this is still the desirable approach," he said.
Nonetheless, Dr. Hercbergs said, "having established the principle that lower thyroid function is favorable, it seems counter-productive to restore normal function while giving chemotherapy. It is like stepping on the brake, when you have the accelerator pressed to the floor."
Tom[a]
