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Thyroid Cancer Treatment (PDQ®)

Stage IV Papillary and Follicular Thyroid Cancer

The most common sites of metastases are lymph nodes, lung, and bone. Treatment of lymph node metastases alone is often curative. Treatment of distant metastases is usually not curative but may produce significant palliation.

Standard treatment options for iodine-sensitive thyroid cancer:

  • I131: Metastases that demonstrate uptake of this isotope may be ablated by therapeutic doses of I131.

Standard treatment options for iodine-resistant thyroid cancer:

  1. Thyroid-stimulating hormone suppression with thyroxine is effective in many lesions not sensitive to I131.
  2. Sorafenib: A phase III randomized, double-blind, placebo-controlled study (DECISION [NCT00984282]) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor, in patients with progressive iodine-refractory differentiated thyroid cancer.[1] In the trial, 417 patients with locally advanced or metastatic radioactive iodine-refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated varieties) who had progressed within the past 14 months were randomly assigned to sorafenib (400 mg twice daily) versus placebo. Prior chemotherapy, thalidomide, or targeted therapy were excluded.[1][Level of evidence: 1iDiii]
    • The median progression-free survival in the sorafenib versus placebo groups was 10.8 versus 5.8 months (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.45–0.76; P < .001).
    • Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; P = .14, one-sided P-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed.
    • Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; P < .001).
    • Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.
  3. Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I131.
  4. External-beam radiation therapy for patients with localized lesions that are unresponsive to I131.[2]

Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

  • Clinical trials evaluating new treatment approaches to this disease should also be considered for these patients. Chemotherapy has been reported to produce occasional complete responses of long duration.[3-5] Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[6][Level of evidence: 2Dii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV papillary thyroid cancer and stage IV follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


  1. Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014. [PUBMED Abstract]
  2. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978. [PUBMED Abstract]
  3. Gottlieb JA, Hill CS Jr, Ibanez ML, et al.: Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30 (3): 848-53, 1972. [PUBMED Abstract]
  4. Harada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. Am J Surg 122 (1): 53-7, 1971. [PUBMED Abstract]
  5. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [PUBMED Abstract]
  6. Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008. [PUBMED Abstract]
  • Updated: February 25, 2015