Expanding indications for recombinant human TSH in thyroid cancer.

On December 17, 2007, Genzyme Corporation (Cambridge, MA) announced that the U.S. Food and Drug Administration (FDA) had approved a supplemental indication for Thyrogen®, its brand of recombinant human thyroid-stimulating hormone (rhTSH), to be used in combination with radioiodine to ablate, or destroy, the remaining thyroid tissue in patients who have had surgery for differentiated thyroid cancer. Although rhTSH was first approved for clinical use in the United States, most European and certain Asian and South American countries approved rhTSH for ablation of postsurgical thyroid remnants before the FDA action. In this article we review the timelines for rhTSH approval and present the views of experts from around the world regarding the expanding indications for rhTSH in thyroid cancer.* The commentary concludes with an editorial summary. Timelines for rhTSH Approval† On November 30, 1998, the FDA issued its first approval of rhTSH, as “an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with thyroid cancer” (1). In the original approval, provisions were made for thyroid cancer patients who were unable to mount an endogenous TSH response to hypothyroidism, such as those with pituitary failure. On September 3, 2000, rhTSH was approved in European Union countries‡ for preparation of Tg testing with or without radioiodine imaging for detection of thyroid remnants and well-differentiated thyroid cancer in adult postthyroidectomy patients maintained on hormone suppression therapy. Low-risk patients with well-differentiated thyroid carcinoma who have undetectable serum Tg levels on thyroid hormone suppression could be followed by assaying rhTSH-stimulated serum Tg levels. These indications were adopted in a similar time period by Liechtenstein, Norway, and Iceland, and similar indications were approved by Ukraine on May 17, 2004. On February 23, 2005, rhTSH was approved in Europe for pretherapeutic stimulation and low-risk postthyroidectomy adult patients maintained on hormone suppression therapy for the ablation of thyroid remnant tissue in combination with 3.7 GBq (100 mCi) radioactive iodine (RAI). In Australia (2006), Malaysia (2007), Thailand (2007), and Singapore (2007), government agencies approved indications for rhTSH similar to that adapted by the FDA in 2007. As noted by Dr. Yamashita, rhTSH has not been approved for clinical use in Japan. Prior to the approval of rhTSH for remnant ablation in 2007, the FDA approved label changes on March 11, 2004, and January 1, 1006. These dealt with Thyrogen® Tg testing alone and in combination with radioiodine imaging in patients with metastatic disease and a Quality of Life statement, respectively. In 2006 rhTSH was approved for clinical use by many countries in South America (see below).