ArticleThe Journal of clinical endocrinology and metabolism2011
Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies.
Article in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Sorafenib in metastatic thyroid cancer: a systematic review.The oncologist · 2014Pooled it
- Pooled it
- Phase I/II Trial of Vandetanib and Bortezomib in Adults with Locally Advanced or Metastatic Medullary Thyroid Cancer.The oncologist · 2019Trial
- Mechanism of and research progress on alterations in the RET gene in thyroid cancer (Review).Molecular medicine reports · 2026Review
- Cytotoxic Effects of Sorafenib, Lapatinib, and Bevacizumab, Alone and in Combination, on Medullary Thyroid Carcinoma Cells.Current oncology (Toronto, Ont.) · 2025Article
- A computational approach to assessing the prognostic implications of BRAF and RAS mutations in patients with papillary thyroid carcinoma.Endocrine · 2024Article
- Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.American journal of cancer research · 2024Review
- AMGDTI: drug-target interaction prediction based on adaptive meta-graph learning in heterogeneous network.Briefings in bioinformatics · 2023Article
- Targeted Therapies in Pheochromocytoma and Paraganglioma.The Journal of clinical endocrinology and metabolism · 2022Review
- Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine.Frontiers in endocrinology · 2022Review
- Nursing Management and Adverse Events in Thyroid Cancer Treatments with Tyrosine Kinase Inhibitors. A Narrative Review.Cancers · 2021Review
- Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis.European thyroid journal · 2021Article
- Update on the systemic management of radioactive iodine refractory differentiated thyroid cancer (Review).Molecular and clinical oncology · 2021Review
- Update on Targeted Therapy in Medullary Thyroid Cancer.Frontiers in endocrinology · 2021Review
- Calcitonin as a biomarker of C cell disease: recent achievements and current challenges.Endocrine · 2020Review
- The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell lines.Journal of endocrinological investigation · 2019Article
- Gastrin inhibits gastric cancer progression through activating the ERK-P65-miR23a/27a/24 axis.Journal of experimental & clinical cancer research : CR · 2018Article
- Genetic and Epigenetic of Medullary Thyroid CancerIranian biomedical journal · 2018Article
- Targeted Therapy for Medullary Thyroid Cancer: A Review.Frontiers in oncology · 2017Review
- Recent advances in the biology and therapy of medullary thyroid carcinoma.F1000Research · 2017Review
Corrections and comments
- Erratum issuedBusaidy, Naifa L [added]; El Naggar, Alder K [corrected to El Naggar, Adel K]
- Erratum issued
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
purposeRas/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins. PATIENTS AND
methodsWe treated 35 patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in a phase I trial. Sorafenib and tipifarnib were given for 21 d with 7 d rest in each 28-d cycle.
resultsWe enrolled 22 patients with metastatic DTC (16 papillary, five follicular, and one poorly differentiated) and 13 patients with MTC, of whom 15 with DTC and 10 with MTC reached first restaging. When tissue was available, eight of 15 DTC patients (53%) had B-Raf mutations; eight of 13 MTC (61.5%) patients had RET mutations. MTC partial response rate was 38% (five of 13) (duration = 9+, 12, 13, 16+, and 34+ months), stable disease of at least 6 months was 31% (four of 13). The DTC partial response rate was 4.5% (one of 22), and stable disease of at least 6 months was 36% (eight of 22). Median progression-free survival for all 35 patients was 18 months (95% confidence interval, 14.6 to not reached months). Median overall survival has not been reached, with a median follow-up of 24 months with 80% overall survival. Grade 1-2 toxicities were mainly rash, fatigue, and diarrhea. The most common grade 3-4 toxicities were rash, rise in amylase/lipase, and fatigue.
conclusionsInhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.