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Thyroid Carcinoma

Which targeted drugs are approved for use in thyroid cancer?

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Key concept

Systemic therapy with oral kinase inhibitors can be used to treat patients with metastatic thyroid cancer that is not amenable to surgical resection or radiation therapy or is refractory to radioactive iodine (RAI).1

Clinical scenario

A 65-year-old man was diagnosed with follicular thyroid cancer 8 years ago. He underwent thyroidectomy followed by RAI. His thyroglobulin has been rising and is unresponsive to RAI. The patient undergoes CT scan which demonstrates multiple bilateral lung nodules that are slowly progressive. He reports mild cough and shortness of breath on exertion.

Action items
  • Lenvatinib and sorafenib are recommended for treatment of patients with radioiodine-refractory differentiated thyroid carcinoma2,3

  • Vandetanib and cabozantinib are recommended for the treatment of medullary carcinoma4,5

Discussion

The main histological subtypes of thyroid carcinoma are:

  • Differentiated (papillary, follicular, Hurthle cell)

  • Medullary

  • Anaplastic

Age is the most important prognostic factor. Patients <45 years old with differentiated thyroid cancer are considered to have stage II disease even in the presence of metastasis.

Thyroid-stimulating hormone suppression by giving levothyroxine is used to control differentiated thyroid cancers.

Patients with slowly progressive asymptomatic metastatic disease may be observed. Oral tyrosine kinase inhibitors (TKIs) have been shown to improve progression-free survival without an overall survival advantage compared to placebo.

Patients can have significant toxicity from oral TKIs, including hypertension, fatigue, rash, diarrhea, and cytopenias.

Pearls
  • Anaplastic thyroid cancer is a rare, very aggressive tumor seen in older individuals

  • Patients with unresectable or metastatic disease can be treated with cytotoxic chemotherapy such as doxorubicin alone or in combination

References
  1. NCCN guidelines for thyroid cancer. Available at: https://www.nccn.org.

  2. Schlumberger M, Tahara M, Wirth L, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372:621-30.

  3. Brose M, Nutting C, Jarzab B, et al. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet 2014;384:319-28.

  4. Wells SA, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30 (2):134-41.

  5. Elisei R, Schlumberger M, Muller S, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 2013;29:3639-46.

Metastatic Cutaneous Melanoma

How do I treat a patient with metastatic cutaneous melanoma?

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Key concept

Cytotoxic chemotherapy is associated with modest activity in metastatic melanoma. A better understanding of the disease biology has led to the emergence of targeted therapy (BRAF and MEK inhibitors) and immunotherapy (anti-PD1 alone or with anti-CTLA4) that have proved their clinical superiority to chemotherapy.

Clinical scenario

A 50-year-old white woman with a history of stage IA melanoma 3 years previously, treated with wide local excision, presents with increased shortness of breath. Her chest CT reveals numerous bilateral lung nodules, the largest one 4 cm in size. Biopsy of one ...

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