Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer

Francis Worden, Martin Fassnacht, Yuankai Shi, Tatiana Hadjieva, Françoise Bonichon, Ming Gao, Laura Fugazzola, Yuichi Ando, Yasuhisa Hasegawa, Do Joon Park, Young Kee Shong, Johannes W.A. Smit, John Chung, Christian Kappeler, Gerold Meinhardt, Martin Schlumberger, Marcia S. Brose

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28 Scopus citations


Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time.

Original languageEnglish
Pages (from-to)877-887
Number of pages11
JournalEndocrine-Related Cancer
Issue number6
StatePublished - Dec 2015


  • Adverse events
  • Differentiated thyroid cancer
  • Sorafenib
  • Targeted therapy
  • Tyrosine kinase inhibitor

Cite this

Worden, F., Fassnacht, M., Shi, Y., Hadjieva, T., Bonichon, F., Gao, M., Fugazzola, L., Ando, Y., Hasegawa, Y., Park, D. J., Shong, Y. K., Smit, J. W. A., Chung, J., Kappeler, C., Meinhardt, G., Schlumberger, M., & Brose, M. S. (2015). Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. Endocrine-Related Cancer, 22(6), 877-887.