scholarly journals Medullary thyroid cancer treated with vandetanib: predictors of a longer and durable response

2020 ◽  
Vol 27 (2) ◽  
pp. 97-110 ◽  
Author(s):  
Laura Valerio ◽  
Valeria Bottici ◽  
Antonio Matrone ◽  
Paolo Piaggi ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Durable Response ◽  
Medullary Thyroid ◽  
Symptomatic Disease ◽  
Younger Age ◽  
Significant Difference

Vandetanib is an important treatment option for advanced metastatic medullary thyroid cancer. The aims of this study were to evaluate the predictors of both a longer response to vandetanib and the outcome. Medical records of 79 medullary thyroid cancer patients treated with vandetanib at our center were analysed. Twenty-five patients were treated for <12 months, 54 were treated for ≥12 months and 24 of these latter were treated for ≥48 months (short-, long- and very long-term). The median progression free survival of the long and very long-term treated patients was significantly longer than in the ZETA trial. When comparing the groups of short - and long-term treated patients the only significant difference was that these latter were less frequently previously treated with a tyrosine kinase inhibitor. However, the long-term treated patients had a younger age, both at diagnosis and enrolment, which was statistically significant in the very long-term treated patients. In the long-term treated group, younger age, enrolment for symptoms and development of adverse events were significantly correlated with a better outcome. The enrolment for symptoms remained the only statistically significant predictor of a good outcome in the very long-term treated patients. In conclusion, early treatment with vandetanib, when patients are younger, with a good ECOG performance status and symptomatic disease, not necessarily progressing for RECIST, seem to be the best predictors of a longer and durable response. Further studies are needed to confirm these results.

scholarly journals Apoferritin/Vandetanib Association Is Long-Term Stable but Does Not Improve Pharmacological Properties of Vandetanib

2021 ◽  
Vol 22 (8) ◽  
pp. 4250
Author(s):  
Kateřina Jáklová ◽  
Tereza Feglarová ◽  
Simona Rex ◽  
Zbyněk Heger ◽  
Tomáš Eckschlager ◽  
...  
Keyword(s):  
Cell Lines ◽  
Targeted Delivery ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Medullary Thyroid ◽  
Long Term Stability ◽  
Carcinoma Cell Lines ◽  
Average Size ◽  
Thyroid Carcinoma Cell

A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Herein, we constructed a nanocarrier based on apoferritin associated with Van (ApoVan). Based on the characteristics obtained by analyzing the average size, the surface ζ-potential and the polydispersive index, ApoVan nanoparticles exhibit long-term stability and maintain their morphology. Experiments have shown that ApoVan complex is relatively stable during storage. It was found that Van is gradually released from its ApoVan form into the neutral environment (pH 7.4) as well as into the acidic environment (pH 6.5). The effect of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines revealed that both forms were toxic in both used cell lines, and minimal differences between ApoVan and Van were observed. Thus, we assume that Van might not be encapsulated into the cavity of apoferritin, but instead only binds to its surface.

scholarly journals The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

2007 ◽  
Vol 67 (14) ◽  
pp. 6956-6964 ◽  
Author(s):  
Nagako Akeno-Stuart ◽  
Michelle Croyle ◽  
Jeffrey A. Knauf ◽  
Roberta Malaguarnera ◽  
Donata Vitagliano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Medullary Thyroid ◽  
Calcitonin Gene ◽  
Thyroid Cancer Cells

Efficacy of selpercatinib after prior systemic therapy in patients with RET mutant medullary thyroid cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6074-6074
Author(s):  
Lori J. Wirth ◽  
Eric Jeffrey Sherman ◽  
Daniela Weiler ◽  
Maria E. Cabanillas ◽  
Bruce Robinson ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Systemic Therapy ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Case Reports ◽  
Objective Response ◽  
Previous Response ◽  
Medullary Thyroid ◽  
Prior Therapy ◽  
Altered Thyroid

6074 Background: Selpercatinib is a first-in-class, CNS active, highly selective, and potent RET kinase inhibitor which has demonstrated durable antitumor activity in patients (pts) with RET altered thyroid cancer and is approved in multiple countries for the treatment of RET fusion+ lung or thyroid cancers. As response rates to cancer therapy usually decline on subsequent lines of therapy, the efficacy of selpercatinib was examined in the context of the last prior therapy received before trial enrollment. Methods: Pts with RET mutant medullary thyroid cancer (MTC) previously treated with multikinase inhibitors (cabozantinib and/or vandetanib) were enrolled in the global LIBRETTO-001 trial (NCT03157128). This post-hoc exploratory intrapatient analysis, based on March 30, 2020 data cutoff date, was performed to compare the retrospective physician-reported objective response rate (ORR) from the last systemic therapy prior to enrollment, as reported in pts case reports, to ORR by independent review committee per RECIST 1.1 with selpercatinib treatment, with each patient serving as his/her own control. Results: Efficacy-evaluable pts, 64% male, 90% white with a median age of 58 years, received prior therapy for MTC (n = 143). Pts had a median of 2 (range 1-8) prior systemic regimens. The ORR on selpercatinib (69%) was markedly higher than for the last prior therapy (10%) received before enrollment. ORR improvements with selpercatinib were observed regardless of prior therapy: cabozantinib (66% vs 14%) or vandetanib (71% vs 12%). Fewer pts had progressive disease as their best overall response with selpercatinib (2/143; 1.4%) compared to last prior therapy (33/143; 23.1%). Notably selpercatinib achieved 62% ORR in pts that did not respond to their previous line of therapy prior to enrolment. This shift from non-responder to responder on selpercatinib therapy was consistent regardless of prior cabozantinib or vandetanib treatment, where pts achieved 57% and 61% ORR respectively when subsequently treated with selpercatinib. In contrast, only 3% of patients did not respond to selpercatinib after a previous response to the immediate prior therapy. Similarly, 5% and 2% of patients were non-responders on selpercatinib after a prior response with cabozantinib and vandetanib therapy respectively. Conclusions: Prior to selpercatinib, response with previous multikinase therapy was rare. By contrast, selpercatinib demonstrated robust efficacy regardless of response to or specific prior therapy in pts with RET mutant MTC. Clinical trial information: NCT03157128.

scholarly journals Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S6197 ◽  
Author(s):  
Hari Deshpande ◽  
Sanziana Roman ◽  
Jaykumar Thumar ◽  
Julie Ann Sosa
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Good Choice ◽  
Phase Ii Trials ◽  
Medullary Thyroid

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer.

scholarly journals Diagnostics of medullary thyroid cancer and the strategy of its management in the absence of biochemical remission

2011 ◽  
Vol 57 (6) ◽  
pp. 45-51
Author(s):  
D O Gazizova ◽  
D G Bel'tsevich ◽  
A N Tiul'pakov ◽  
O V Simakina ◽  
T V Soldatova
Keyword(s):  
Thyroid Cancer ◽  
Early Diagnosis ◽  
Successful Treatment ◽  
Medullary Thyroid Cancer ◽  
Diagnostic Techniques ◽  
Term Treatment ◽  
Medullary Thyroid ◽  
Long Term Treatment ◽  
Biochemical Remission

Early diagnosis greatly facilitates successful treatment of medullary thyroid cancer. The present paper is designed to report the results of analysis of the studies carried out with the use of various diagnostic techniques and the data obtained during the long-term treatment of the patients with this pathology in the absence of biochemical remission.

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