A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer.
BACKGROUND
Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that has been shown to induce differentiation, cell cycle arrest, and apoptosis in a variety of human cancers including thyroid cancer.


METHODS
Ten patients with differentiated thyroid cancer were enrolled in an open-label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week, then 8 mg daily for 7 weeks). The levels of PPARgamma receptor mRNA and protein expression were determined in the patient's neoplasm.


RESULTS
Of 10 patients, 4 had positive radioiodine scans after rosiglitazone therapy with uptake in the neck in 3 patients and in the pelvis in 1 patient. After treatment, the serum thyroglobulin level decreased in 2 patients, increased in 5 patients, and was stable in 3 patients. No patient developed clinically important toxicity associated with rosiglitazone treatment. We found no relationship in the level of PPARgamma mRNA and protein expression in patients who had radioiodine uptake compared with those who did not.


CONCLUSIONS
Our findings suggest that rosiglitazone treatment may induce radioiodine uptake in some patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. We found no relationship between the expression level of the PPARgamma mRNA and protein in the neoplasm and radioiodine uptake status after rosiglitazone therapy, questioning the potential pathway of effect.
Kebebew
Electron
E
Department of Surgery, University of California, San Francisco, CA 94143, USA. kebebewe@surgery.ucsf.edu
Peng
Miao
M
Reiff
Emily
E
Treseler
Patrick
P
Woeber
Kenneth A
KA
Clark
Orlo H
OH
Greenspan
Francis S
FS
Lindsay
Sheila
S
Duh
Quan-Yang
QY
Morita
Eugene
E
D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011877:Radionuclide Imaging; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D013954:Thyroglobulin / Q000097:blood*; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*
D007457:Iodine Radioisotopes; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013954:Thyroglobulin