scholarly journals Lack of Therapeutic Effect of the Histone Deacetylase Inhibitor Vorinostat in Patients with Metastatic Radioiodine-Refractory Thyroid Carcinoma

2009 ◽  
Vol 94 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Jennifer A. Woyach ◽  
Richard T. Kloos ◽  
Matthew D. Ringel ◽  
Daria Arbogast ◽  
Minden Collamore ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Severe Thrombocytopenia ◽  
Minor Bleeding ◽  
Clinical Grade ◽  
Medullary Thyroid ◽  
Advanced Thyroid Cancer ◽  
Grade 3

Abstract Context: Aberrant histone deacetylase activity is seen in a variety of malignancies, and histone deacetylase inhibitors such as vorinostat have been shown to induce cell death and sensitize cells to cytotoxic chemotherapy in thyroid cancer cell lines. This phase II study was undertaken to assess objective response to vorinostat in patients with advanced thyroid cancer. Experimental Design: A total of 19 patients with differentiated thyroid cancer (n = 16) and medullary thyroid cancer (n = 3) were enrolled in the study. Patients received oral vorinostat at a starting dose of 200 mg twice daily, with dose adjustments allowed as necessary for toxicity. Patients were treated for 2 wk, followed by 1 wk off therapy (3-wk cycle) until disease progression or study withdrawal. Responses were measured by Response Evaluation Criteria in Solid Tumors criteria and correlated with tumor markers. Results: No patient achieved a partial or complete response. Median duration of therapy in patients with differentiated thyroid cancer was 17 wk, whereas in medullary thyroid cancer patients it was 25 wk. Reasons for termination included progression of disease by RECIST criteria (n = 7), clinical progression (n = 3), and adverse events (AEs) (n = 9). AEs were primarily grade 1–3; no clinical grade 4 or grade 5 events were observed. Clinical grade 3 AEs consisted of fatigue, dehydration, ataxia, pneumonia, bruises, and deep vein thrombosis. Severe thrombocytopenia was seen in seven patients (grade 3, n = 5; grade 4, n = 2) and was associated with minor bleeding or bruises. Conclusions: Vorinostat at this dose and schedule is not an effective treatment for advanced thyroid cancer.

Phase I trial of combination sorafenib and tipifarnib: The experience in advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 5586-5586 ◽  
Author(s):  
M. E. Cabanillas ◽  
R. Kurzrock ◽  
S. I. Sherman ◽  
A. M. Tsimberidou ◽  
S. Waguespack ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase I ◽  
Differentiated Thyroid Cancer ◽  
Phase I Trial ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

scholarly journals Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Αgainst Medullary Thyroid Cancer?

2016 ◽  
Vol 36 (10) ◽  
pp. 5019-5024 ◽  
Author(s):  
CHRISTOS DAMASKOS ◽  
SERENA VALSAMI ◽  
ELEFTHERIOS SPARTALIS ◽  
EFSTATHIOS A ANTONIOU ◽  
PERIKLIS TOMOS ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid ◽  
Novel Therapeutic

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 6027-6027 ◽  
Author(s):  
Jaume Capdevila ◽  
Jose Manuel Trigo Perez ◽  
Javier Aller ◽  
Jose Luis Manzano ◽  
Silvia Garcia Adrian ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

scholarly journals Evidence that polymorphisms in detoxification genes modulate the susceptibility for sporadic medullary thyroid carcinoma

2012 ◽  
Vol 166 (2) ◽  
pp. 241-245 ◽  
Author(s):  
R B Barbieri ◽  
N E Bufalo ◽  
R Secolin ◽  
A C N Silva ◽  
L V M Assumpção ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Stepwise Regression ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Cell Cycle Control ◽  
Control Group ◽  
Healthy Individuals ◽  
Medullary Thyroid ◽  
Low Penetrance Genes

AimPolymorphic low-penetrance genes have been consistently associated with the susceptibility to a series of human tumors, including differentiated thyroid cancer.MethodsTo determine their role in medullary thyroid cancer (MTC), we used TaqMan SNP method to genotype 47 sporadic MTC (s-MTC) and a control group of 578 healthy individuals for CYP1A2*F, CYP1A1m1, GSTP1, NAT2 and 72TP53. A logistic regression analysis showed that NAT2C/C (OR=3.87; 95% CI=2.11–7.10; P=2.2×10−5) and TP53C/C genotypes (OR=3.87; 95% CI=1.78–6.10; P=2.8×10−4) inheritance increased the risk of s-MTC. A stepwise regression analysis indicated that TP53C/C genotype contributes with 8.07% of the s-MTC risk.ResultsWe were unable to identify any relationship between NAT2 and TP53 polymorphisms suggesting they are independent factors of risk to s-MTC. In addition, there was no association between the investigated genes and clinical or pathological features of aggressiveness of the tumors or the outcome of MTC patients.ConclusionIn conclusion, we demonstrated that detoxification genes and apoptotic and cell cycle control genes are involved in the susceptibility of s-MTC and may modulate the susceptibility to the disease.

Safety of denosumab in patients with refractory differentiated thyroid cancer and advanced medullary thyroid cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17578-e17578 ◽  
Author(s):  
Johanna Wassermann ◽  
Elise Mathy ◽  
Geraldine Lescaille ◽  
Marine Slim ◽  
Camille Buffet ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Calcium Supplementation ◽  
Osteonecrosis Of The Jaw ◽  
Treatment Benefit ◽  
Medullary Thyroid ◽  
Cervical Surgery

e17578 Background: Few data exist regarding the use of denosumab in patients with bone metastases from radioactive iodine (RAI) refractory differentiated thyroid cancer (DTC) and advanced medullary thyroid cancer (MTC). We aimed to describe adverse events of specific interest - osteonecrosis of the jaw (ONJ) and severe hypocalcemia - in this rare setting. Methods: We retrospectively reviewed the charts of all the patients treated with denosumab for bone metastases from RAI-refractory DTC and advanced MTC in our institution. All patients had a calcium measurement and a clinical and radiological dental screening before denosumab initiation. All patients without hypercalcemia received a calcium supplementation. We assessed associations between ONJ or severe hypocalcemia ( < 1.75mmol/L) and suspected risk factors by Fisher exact tests. Results: Between 2014 and 2018, 23 patients were treated with denosumab. Two-thirds of patients were male (n = 16), median age was 69 years (range 43-87). Histology was DTC and MTC in 19 (83%) and 4 (17%) patients, respectively. DTC patients had received a median cumulated dose (CD) of 300 mCi of RAI (range 100-700). Ten patients (43%) had at least one cervical surgery for recurrence or persistence, and 6 (26%) had cervical radiotherapy. Four patients had hypoparathyroidism before denosumab initiation. Two-thirds of patients ( n =15) received a tyrosine kinase inhibitor (TKI) in association with denosumab. The median duration of denosumab was 20 months (range 1-47). ONJ occurred in 6 patients (26%) and severe hypocalcemia in 3 patients (13%). Conclusions: Patients with RAI-refractory DTC and advanced MTC are at high risk of ONJ and severe hypocalcemia under denosumab treatment. Benefit/risk ratio should be highly weighted particularly when treatment is prolonged. Patients should be closely monitored for the risk of ONJ and hypocalcemia. [Table: see text]

scholarly journals Familial non-medullary thyroid cancer: a critical review

2020 ◽  
Author(s):  
M. Capezzone ◽  
E. Robenshtok ◽  
S. Cantara ◽  
M. G. Castagna
Keyword(s):  
Thyroid Cancer ◽  
Genetic Background ◽  
Differentiated Thyroid Cancer ◽  
Genetic Factors ◽  
Medullary Thyroid Cancer ◽  
Clinical Aspects ◽  
Incomplete Penetrance ◽  
Medullary Thyroid ◽  
Familial Form ◽  
The Moment

Abstract Background Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. Purpose Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.

scholarly journals Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC)

2017 ◽  
Vol 177 (4) ◽  
pp. 309-317 ◽  
Author(s):  
Jaume Capdevila ◽  
José Manuel Trigo ◽  
Javier Aller ◽  
José Luís Manzano ◽  
Silvia García Adrián ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Objective Response ◽  
Cross Resistance ◽  
Second Line ◽  
First Line ◽  
Medullary Thyroid ◽  
First Line Therapy ◽  
Line Therapy

Background Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012–November 2014). Subjects and Methods 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Results Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0–24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1–12.2) (DTC: 7.4 months (95% CI: 3.1–11.8) and MTC: 9.4 months (95% CI: 4.8–13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Conclusion Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.

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