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

Tyrosine kinase inhibitors in differentiated thyroid carcinoma: a review of the clinical evidence

2011 ◽  
Vol 1 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Hendrieke C Hoftijzer ◽  
Ellen Kapiteijn ◽  
Tatiana Schneider ◽  
Guido C Hovens ◽  
Hans Morreau ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Clinical Evidence ◽  
Kinase Inhibitors ◽  
Differentiated Thyroid Carcinoma

scholarly journals More than a Decade of Tyrosine Kinase Inhibitors in the Treatment of Solid Tumors: What We Have Learned and What the Future Holds

2015 ◽  
Vol 10s3 ◽  
pp. BMI.S22436 ◽  
Author(s):  
Maria Vergoulidou
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecules ◽  
Solid Tumors ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Free Treatment

The use of tyrosine kinase inhibitors (TKIs) in the treatment of solid tumors is the expected standard of care for many types of tumors. Since the description of signal transduction pathways, followed by the development of small molecules designed to inhibit those pathways, there has been significant improvement not only in progression-free survival and overall survival but also in aiming toward chemotherapy-free treatment of solid tumors to maximize quality of life. This article reviews available TKIs and discusses toxicity, dosing, and resistance.

Treatment of nonresectable and metastatic gastrointestinal stromal tumors: Experience with the use of tyrosine kinase inhibitors in a third-level hospital in Mexico city.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 224-224
Author(s):  
Abdel Karim Dip Borunda ◽  
Alejandro J. Silva
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stromal Tumors

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

scholarly journals Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer

2019 ◽  
Vol 7 (6) ◽  
pp. 973-977 ◽  
Author(s):  
Maria Carmela Annunziata ◽  
Maria Ferrillo ◽  
Eleonora Cinelli ◽  
Luigia Panariello ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Skin Reaction ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Skin Reactions ◽  
Cutaneous Toxicity ◽  
Common Skin

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth. AIM: In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients. METHODS: We included patients referring from January 2016 to January 2018 affected by lung cancer and under TKIs. We collected data about the clinical exam, clinical photography, dermoscopy, histology and direct microscopic examination for each patient and we performed retrospectively descriptive analyses to assess whether a specific TKIs is linked significantly to particular cutaneous toxicity. RESULTS: The majority of skin toxicities were due to afatinib, and the most common skin reaction was rash. We selected 60 patients with skin reactions, treated by TKIs for lung cancer. The majority of skin toxicities were due to afatinib (47/102 adverse reactions) and erlotinib (39/102). The most common skin reaction was rash (63% of patients), followed by xerosis (30%) and granulomas (30%). There was no significant relationship between a specific type of cutaneous reaction and specific EGFRi except for granulomas, developed more frequently in patients under afatinib (p < 0.05). CONCLUSION: Most of our patients (63%) developed a cutaneous rash under TKIs. Most commonly afatinib was the drug involved, although it wasn’t the most used EGFRi. Moreover, we noticed a significant correlation between afatinib therapy and appearance of granulomas.

Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine-kinase inhibitors (TKIs): A literature-based meta-analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 500-500
Author(s):  
Andreas Demetrios Nearchou ◽  
Antonis Valachis ◽  
Pehr Lind ◽  
Olof Akre ◽  
Per Sandstrom
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Fixed Effects ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
P Value ◽  
Significant Difference

500 Background: The development of hypothyroidism in patients with mRCC during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. The potential role of hypothyroidism as predictive marker of outcome has been studied with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for both progression free (PFS) and overall survival (OS) in patients with mRCC treated with TKI. Methods: We searched PubMed as well as the electronic abstract databases of the major international congresses’ proceedings to identify all eligible studies which reported a correlation of the development of hypothyroidism during treatment with TKI and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis by using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism and patients without hypothyroidism during sunitinib therapy (HR: 0.82, 95% CI: 0.59-1.13, p-value = 0.22) (6 studies; 250 patients). For studies that included patients treated with either sunitinib or sorafenib, the development of hypothyroidism was found to be predictive for longer progression free survival (HR: 0.59, 95% CI: 0.42-0.84, p-value = 0.003) (3 studies; 205 patients). The HR for OS was 0.52 (95% CI: 0.31-0.87, p-value = 0.01) for patients who developed hypothyroidism during sunitinib therapy compared to patients without hypothyroidism (4 studies; 147 patients). Conclusions: The development of hypothyroidism during TKIs therapy is not clearly shown to be predictive in patients with mRCC. The observed advantage in overall survival for patients with treatment related hypothyroidism should be interpreted with caution due to the potential imbalance of treatments received after first line treatment in each group.

Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2

2020 ◽  
Vol 52 (08) ◽  
pp. 588-597 ◽  
Author(s):  
Maran Ilanchezhian ◽  
Sophia Khan ◽  
Christian Okafor ◽  
John Glod ◽  
Jaydira Del Rivero
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Medullary Thyroid Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Multiple Endocrine Neoplasia ◽  
Kinase Inhibitors ◽  
Multiple Endocrine Neoplasia Type ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

AbstractMedullary Thyroid Carcinoma (MTC) is a rare neuroendocrine cancer that accounts for 1–2% of thyroid cancers in the United States (U.S.). While most cases are sporadic, 25% of MTC cases are hereditary. These hereditary cases occur in the setting of Multiple Endocrine Neoplasia Type 2A (MEN2A) or 2B (MEN2B) driven by mutations in the Rearranged during Transfection RET proto-oncogene. This article discusses hereditary MTC in the setting of MEN2 and the treatment options available for it. The first line treatment for this disease is typically a total thyroidectomy and tyrosine kinase inhibitors. Two tyrosine kinase inhibitors, vandetanib and cabozantinib, have been approved for treatment of advanced MTC, but options beyond those are limited. However, several promising treatments are being studied, which are discussed in this review.

EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6014-6017 ◽  
Author(s):  
Mustafa Daghistani ◽  
David Marin ◽  
Jamshid Sorouri Khorashad ◽  
Lihui Wang ◽  
Philippa C. May ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Event Free Survival ◽  
Free Survival

Abstract Activation of the EVI-1 oncogene has been reported in acute myeloid leukemia, chronic myeloid leukemia (CML) in blast crisis, and less commonly, in chronic-phase CML patients. We screened an unselected cohort of 75 chronic-phase CML patients who had failed imatinib for expression of EVI-1 and sought a correlation with subsequent outcome on the second-generation tyrosine kinase inhibitors dasatinib (n = 61) or nilotinib (n = 14). The 8 patients (10.7%) who expressed EVI-1 transcripts detectable by real-time polymerase chain reaction had significantly lower event-free survival, progression-free survival, and overall survival than patients with undetectable transcript. The predictive value of EVI-1 expression was validated in an independent cohort. In a multivariate analysis, EVI-1 expression status and the best cytogenetic response obtained on imatinib were the only independent predictors for overall survival, progression-free survival, and event-free survival. Our data suggest that screening for EVI-1 expression at the time of imatinib failure may predict for response to second-line TKI therapy and consequently aid clinical management.

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