Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis

Castroneves, Luciana A.; Negrão, Marcelo V.; Freitas, Ricardo Miguel Costa de; Papadia, Carla; Lima, Jose Viana; Fukushima, Julia T; Simão, Eduardo Furquim; Kulcsar, Marco Aurélio Vamondes; Tavares, Marcos Roberto; Jorge, Alexander Augusto de Lima; Castro, Gilberto de; Hoff, Paulo M.; Hoff, Ana O.

doi:10.1089/thy.2015.0334

Cited by 40 publications

(26 citation statements)

References 17 publications

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“…We found 614 articles for initial abstract screening and 19 of them were included for full text reading. Following the full‐text screening step, additional 11 studies were excluded and we included 8 studies, comprising of 101 patients with advanced MTCs for final analyses (Figure ) . Table describes the characteristics of all included studies.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta‐analysis

Vuong

Tran

et al. 2019

Head & Neck

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Introduction The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs). Methods We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib‐related AEs were calculated using random‐effect model. Results Eight trials with 101 metastatic MTCs were included for meta‐analyses. The overall PR and SD were 21% (95% CI = 9‐33) and 58% (95% CI = 41‐75), respectively. Hand‐foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs. Conclusion Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.

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Section: Resultsmentioning

confidence: 99%

“…Table describes the characteristics of all included studies. Among the eight included studies, three studies fulfilled the requirements for phase II clinical trial, one study was prospective case series, and the remaining four studies were retrospective . All included trials recruited patients with locally advanced and/or metastatic MTCs.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta‐analysis

Vuong

Tran

et al. 2019

Head & Neck

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“…In a recently published retrospective longitudinal study of 12 patients with progressive metastatic MTC, 10 patients showed stable disease (83.3%), no PR was observed. Median PFS was 9 months (Castroneves et al 2016). These data collectively suggest a possible role for sorafenib in the treatment of progressive, advanced MTC; however, a randomized phase 3 trial is required for rigorous evaluation of safety and efficacy of sorafenib in these patients.…”

Section: Sorafenibmentioning

confidence: 89%

New drugs for medullary thyroid cancer: new promises?

Spitzweg¹,

Morris²,

Bible³

2016

Endocrine-Related Cancer

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Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives.

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“…2013; Elisei et al 2013; Weitzman et al 2015; Tannir et al 2017), lenvatinib (approved for differentiated thyroid carcinoma and renal cell carcinoma) (Matsui et al 2008; Okamoto et al. 2013; Schlumberger et al 2015; Cabanillas et al 2016), ponatinib (approved for chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia) (O'Hare et al 2009; Cortes et al 2012; De Falco et al 2013; Mologni et al 2013; Hoy et al 2014), sunitinib (approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor) (Mendel et al 2003; Mologni et al 2013), regorafenib (approved for colorectal cancer and gastrointestinal stromal tumor) (Ettrich et al 2014;), and sorafenib (approved for differentiated thyroid carcinoma, renal cell carcinoma and hepatocellular carcinoma) (Wilhelm et al 2004; Carlomagno et al 2006; Plaza-Menacho et al 2007; Thomas et al 2014; de Castroneves et al 2016). …”

Section: Clinically Approved Ret Tkismentioning

confidence: 99%

The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer

Falco

Carlomagno

et al. 2017

Best Practice & Research Clinical Endocrinology & Metab

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RET receptor tyrosine kinase (RTK) acts as an ontogenetic driver in several human malignancies, including papillary and medullary thyroid carcinoma, lung adenocarcinoma, colorectal carcinoma, Spitzoid neoplasms, salivary gland carcinoma and chronic myeloproliferative disorders, secondary to as diverse genetic lesions as point-mutations, small insertions/deletions, and gene fusions. In other neoplasms, including breast and pancreatic adenocarcinoma, RET over-expression is up-regulated. Thus, small molecule compounds with RET tyrosine kinase inhibitory activity (TKIs) are being investigated for the targeted treatment of these malignancies. Multi-targeted TKIs with the RET inhibitory enzymatic activity of IC50 in the nanomolar range have entered clinical practice, registered for the treatment of medullary thyroid cancer (vandetanib, cabozantinib), radioiodine refractory non medullary thyroid cancer (lenvatinib, sorafenib) or cancers of other sites (sunitinib, ponatinib, regorafenib). This review summarizes mechanisms of RET oncogenic activity and properties of new TKIs that, at the preclinical stage, have demonstrated promising anti-RET activity.

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Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis

Abstract: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.

Cited by 40 publications

References 17 publications

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta‐analysis

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta‐analysis

New drugs for medullary thyroid cancer: new promises?

The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer

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