Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Advanced Thyroid Cancer

2019 ◽  
Vol 14 (3) ◽  
pp. 226-241
Author(s):  
Emanuela Vaccher ◽  
Ornella Schioppa ◽  
Ferdinando Martellotta ◽  
Giulia Fornasier ◽  
Elisa Giacomin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Anticancer Drugs ◽  
Safety Profile ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Differentiated Thyroid Carcinoma ◽  
Systematic Analysis ◽  
Pharmacovigilance Database ◽  
Advanced Thyroid Cancer

Background: Thyroid cancer is the most common endocrine neoplasia and represents approximately 1.5% to 2.1% of all cancers diagnosed annually worldwide. Iodine Refractory Differentiated Thyroid Carcinoma (RR-DTC) and advanced/metastatic medullary thyroid carcinoma are relatively uncommon yet prognostically significant thyroid cancers. Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers, including thyroid cancer. Many Multi-Kinase Inhibitors (MKIs) which are now FDA-/EMA approved for thyroid cancer have shown clinical benefit in patients with advanced cancer. Treatmentrelated toxicities occur frequently with these drugs and can be severe or life-threatening. Objective: This review summarizes the role of targeted therapy with MKIs in the management of RRDTC and advanced/metastatic MTC patients, focusing on side-effect profiles of these drugs, with a presentation of several recent patents published in this field. Methods: We review the scientific literature on advanced thyroid cancer and analyze the International Pharmacovigilance database (FAERS, Eudravigilance, and WHO Vigibase) for adverse drug reactions. Results: This systematic analysis highlights the difference in the safety profile of the recent drugs used in the treatment of advanced thyroid cancer and the recent discoveries for diagnosis or treatment of the thyroid cancer. Conclusion: It is essential to investigate the safety profile of recent anticancer drugs for advanced thyroid cancer to allow health professionals to make the best choice for each patient by conducting risk/benefit assessment.

scholarly journals Lenvatinib Administered via Nasogastric Tube in Poorly Differentiated Thyroid Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Eleonora Molinaro ◽  
David Viola ◽  
Nicola Viola ◽  
Pierpaolo Falcetta ◽  
Francesca Orsolini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Gastric Tube ◽  
Kinase Inhibitors ◽  
Locally Advanced ◽  
Differentiated Thyroid Carcinoma ◽  
Cervical Esophagus ◽  
Extrinsic Compression ◽  
Poorly Differentiated ◽  
Iodine 131

Background. The tyrosine kinase inhibitors (TKIs) are indicated for the treatment of locally advanced or metastatic progressive thyroid carcinoma (CDT), refractory to radioactive iodine. The following report describes the efficacy of lenvatinib administered through a nose-gastric tube (SNG) in a patient affected with a poorly differentiated thyroid carcinoma (PDTC) which determined a stenosis of the esophagus. Material and Methods. A patient was followed up for papillary thyroid carcinoma follicular variant (T3NxMx), subjected to total thyroidectomy and treated with iodine-131 radio metabolic therapy. Two years after surgery, following the onset of dysphonia and dysphagia, patient was submitted to a computed tomography (CT) scan of the neck that showed the presence of a lesion of 6 × 2.5 × 3.5 cm, which determined trachea deviation and cervical esophagus compression. The biopsy indicated the presence of PDTC, triggering tracheal lumen reduction and sub-stenosis of the cervical esophagus for an ab-extrinsic compression. A nose-gastric tube (SNG) was placed and lenvatinib was started at a dose of 20 mg/day, administered via this probe after opening the capsules and diluting the drug in 10 ml of saline solution. Results. One month later, CT showed a significant cervical lesion reduction. Bronchoscopy confirmed tracheal infiltration, but the residual caliber was improved from 50% to 75%. At the esophagogastroduodenoscopy (EGDS), the sub stenosis of the cervical esophagus was no longer appreciated; however, a double perforation of the esophagus was found, without fistula. Conclusion. Lenvatinib therapy is effective also when administered via SNG. Our result is of particular relevance in the management of thyroid cancer patients, especially in the presence of subjects unable to swallow. Further studies are needed to validate the administration of lenvatinib by SNG, in order to extend the indications to this alternative administration way, beside the oral one.

scholarly journals Current and Future Perspectives in Thyroid Carcinoma Treatment

2013 ◽  
Vol 09 (02) ◽  
pp. 171 ◽  
Author(s):  
José Manuel Gómez-Sáez ◽  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Adjuvant Chemoradiotherapy

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Postoperative131I remnant ablation is used to eliminate the postsurgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low131I dose, 30 mCi, for postoperative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multitargeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib, and cabozantinib are multikinase inhibitors that have the ability of inhibiting the rearranged during transection (RET) and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carcinoma is often advanced and metastatic at diagnosis. Patients with localized disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

scholarly journals Current and Future Perspectives in Thyroid Carcinoma Treatment

2010 ◽  
Vol 9 (1) ◽  
pp. 22
Author(s):  
José Manuel Gómez Sáez ◽  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Adjuvant Chemoradiotherapy ◽  
Differentiated Thyroid Cancers

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Post-operative131I remnant ablation is used to eliminate the post-surgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low131I dose, 30 mCi, for post-operative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multi-targeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib and cabozantinib are multi-kinase inhibitors that have the ability of inhibiting the rearranged during transection(RET)and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carinoma is often advanced and metastatic at diagnosis. Patients with localised disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

scholarly journals New perspectives on the treatment of differentiated thyroid cancer

2007 ◽  
Vol 51 (4) ◽  
pp. 612-624 ◽  
Author(s):  
Sabrina Mendes Coelho ◽  
Denise Pires de Carvalho ◽  
Mário Vaisman
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
New Drugs ◽  
In Vivo Studies ◽  
Advanced Thyroid Cancer

Even though differentiated thyroid carcinoma is a slow growing and usually curable disease, recurrence occurs in 20-40% and cellular dedifferentiation in up to 5% of cases. Conventional chemotherapy and radiotherapy have just a modest effect on advanced thyroid cancer. Therefore, dedifferentiated thyroid cancer represents a therapeutic dilemma and a critical area of research. Targeted therapy, a new generation of anticancer treatment, is planned to interfere with a specific molecular target, typically a protein that is believed to have a critical role in tumor growth or progression. Since many of the tumor-initiation events have already been identified in thyroid carcinogenesis, targeted therapy is a promising therapeutic tool for advanced thyroid cancer. Several new drugs are currently being tested in in vitro and in vivo studies and some of them are already being used in clinical trials, like small molecule tyrosine kinase inhibitors. In this review, we discuss the bases of targeted therapies, the principal drugs already tested and also options of redifferentiation therapy for thyroid carcinoma.

scholarly journals Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives

2021 ◽  
Vol 53 (03) ◽  
pp. 149-160
Author(s):  
Frederik A. Verburg ◽  
Holger Amthauer ◽  
Ina Binse ◽  
Ingo Brink ◽  
Andreas Buck ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Placebo Treatment ◽  
Differentiated Thyroid Carcinoma ◽  
Future Research ◽  
Prospective Comparison

AbstractNotwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

scholarly journals Tyrosine-kinase inhibitors to treat radioiodine-refracted, metastatic, or recurred and progressive differentiated thyroid carcinoma [Review]

2016 ◽  
Vol 63 (7) ◽  
pp. 597-602 ◽  
Author(s):  
Yasuhiro Ito ◽  
Shinichi Suzuki ◽  
Ken-ichi Ito ◽  
Tsuneo Imai ◽  
Takahiro Okamoto ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Differentiated Thyroid Carcinoma

scholarly journals Brain Metastases From Differentiated Thyroid Carcinoma: Prevalence, Current Therapies, and Outcomes

2018 ◽  
Vol 3 (2) ◽  
pp. 359-371 ◽  
Author(s):  
Cristiane J Gomes-Lima ◽  
Di Wu ◽  
Sarika N Rao ◽  
Sree Punukollu ◽  
Rama Hritani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Brain Metastases ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Differentiated Thyroid Carcinoma ◽  
Unusual Site ◽  
Current Therapies ◽  
The Brain

Abstract Background and Objective The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. Methods We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. Results From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). Conclusion The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

2020 ◽  
Author(s):  
Joachim Alexandre ◽  
Joe-Elie Salem ◽  
Javid Moslehi ◽  
Marion Sassier ◽  
Camille Ropert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Anticancer Drugs ◽  
Kinase Inhibitors ◽  
Descriptive Analysis ◽  
Individual Case ◽  
World Health ◽  
European Medicines Agency ◽  
Individual Case Safety Report ◽  
Pharmacovigilance Database ◽  
Haematologic Malignancies

Abstract Aims The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF. Methods and results A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody. Conclusion Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.

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