Drug therapy alternatives in the treatment of thyroid cancer.

Therapy of thyroid cancers is based on the removal of the primary disease by surgery, replacement of the hormonal deficiencies and subsequent therapy of the recurrent and metastatic disease. The metabolic characteristics of many thyroid tumors mean that radionuclide techniques have been used in the identification of sites of tumour and their subsequent therapy. Differentiated thyroid cancers, papillary, follicular and mixed papillary follicular, are treated by surgery--usually a total or subtotal thyroidectomy. Postoperatively, patients have thyroxine as a replacement therapy and to suppress thyroid-stimulating hormone production. Radioiodine therapy is often given to ablate the thyroid remnant. This allows (a) adequate follow-up of patients using thyroglobulin measurements and assessment scans as necessary, and (b) further therapy with radioiodine for metastatic disease. Patients with a short effective half-life of radioiodide may require higher activities or pharmacological methods of prolonging the retention half-times of iodine. The use of chemotherapy in this group of tumors is limited and at best provides palliation. The overall prognosis is good for differentiated thyroid cancer; papillary carcinomas have an 80 to 90% 10-year survival, whereas follicular tumors are associated with a 65 to 75% 10-year survival. Medullary carcinomas may be sporadic or familial, and some of the latter form part of a multiple endocrine neoplasia syndrome (MEN). Primary treatment is surgery, and total thyroidectomy is usually recommended since tumours are often multifocal. The use of radiolabelled metaiodobenzylguanidine (MIBG) and 111In octreotide as potential therapeutic agents has been explored and may be potentially useful in palliative care. Chemotherapy is of limited benefit. The 10-year survival for medullary carcinomas is 60 to 70%. Anaplastic tumours of the thyroid are usually aggressive, with a high mortality. Treatment is palliative by surgical debulking; some patients may benefit from local radiotherapy or occasionally chemotherapy. The use of therapeutic doses of radionuclides is well tolerated, although it may be associated with a variety of mostly transient adverse effects, including gastritis, thyroiditis and sialadenitis. Therapy with high activities of radioiodine require radiation protection precautions. Despite retreatment with radioiodine there appear to be no long term effects on the fertility of patients, and healthy children are born to women receiving this treatment. 131I remains perhaps the most specific cancer therapy available today and has few adverse effects. It is difficult to see any marked improvement being developed for differentiated thyroid cancer, with the possible exception of targeted gene therapy.