Sorafenib for the treatment of thyroid cancer: an updated review
Jolanta Krajewska1, Daria Handkiewicz-Junak, Barbara Jarzab
1Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Nuclear Medicine and Endocrine Oncology Department, Gliwice Branch , Gliwice , Poland + 48 32 2789301 ; +48 32 2789310 ; bjarzab@io.gliwice.pl.
Introduction:
Sorafenib (Nexavar) is an oral multi-kinase inhibitor targeting B-type Raf kinase (BRAF) (both wild type and BRAF(V600E)), VEGFR1, VEGFR2, VEGFR3, PDGFRβ and RET (also RET/PTC) influencing both differentiated thyroid cancer (DTC) cell proliferation and angiogenesis.
Areas Covered:
Encouraging results achieved in numerous Phase II trials were confirmed in a Phase III study conducted in radioiodine-refractory DTC. Sorafenib compared to placebo significantly prolongs progression-free survival, 10.8 versus 5.8 months, respectively. However, its administration resulted mainly in disease stabilization. No complete remission was obtained in any study. Beneficial effects were also demonstrated for medullary and anaplastic thyroid cancer; however further studies fulfilling evidence based medicine criteria are necessary. Its toxicity profile is convergent with other VEGFR inhibitors. The most common treatment-related side-effects involve skin toxicity (predominantly hand-foot skin reaction, different rashes and alopecia), gastrointestinal disturbances (diarrhea, abdominal pain), constitutional adverse reactions (anorexia, weight loss, fatigue) and hypertension. Although most adverse reactions are manageable, > 50% of patients required dose reduction.
Expert Opinion:
Sorafenib constitutes the first line treatment option in advanced, radioiodine-refractory DTC. However, there are still no data on its efficacy in patients progressed after another tyrosine kinase inhibitor. Other applications of the drug, such as use as adjuvant therapy to 131-I treatment, requires further studies.
Insights
Sorafenib is a first-line treatment for advanced differentiated thyroid cancer (DTC) that is refractory to radioiodine, significantly prolonging progression-free survival. While effective for disease stabilization, further research is needed for other thyroid cancer types and adjuvant therapies.
Area of Science:
- Oncology
- Pharmacology
- Endocrinology
Background:
- Sorafenib (Nexavar) is an oral multi-kinase inhibitor targeting BRAF, VEGFR, PDGFRβ, and RET.
- It influences both differentiated thyroid cancer (DTC) cell proliferation and angiogenesis.
Purpose of the Study:
- To evaluate the efficacy and safety of Sorafenib in radioiodine-refractory DTC.
- To explore its potential in other thyroid cancer subtypes and as adjuvant therapy.
Main Methods:
- Phase III clinical trial comparing Sorafenib to placebo in radioiodine-refractory DTC.
- Analysis of progression-free survival and adverse events.
Main Results:
- Sorafenib significantly prolonged progression-free survival (10.8 vs. 5.8 months) compared to placebo.
- Disease stabilization was the primary outcome; no complete remissions were observed.
- Common side effects include skin toxicity, gastrointestinal issues, fatigue, and hypertension, often requiring dose reduction.
Conclusions:
- Sorafenib is the first-line treatment for advanced, radioiodine-refractory DTC.
- Efficacy in patients progressed after other tyrosine kinase inhibitors requires further investigation.
- Additional studies are needed to assess its use as adjuvant therapy to 131-I treatment.
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