scholarly journals Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Thyroid ◽  
2017 ◽  
Vol 27 (9) ◽  
pp. 1142-1148 ◽  
Author(s):  
Yasuhiro Ito ◽  
Naoyoshi Onoda ◽  
Ken-ichi Ito ◽  
Iwao Sugitani ◽  
Shunji Takahashi ◽  
...  



2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6019-6019 ◽  
Author(s):  
Dapeng Li ◽  
Ping Zhang Tang ◽  
Xiaohong Chen ◽  
Minghua Ge ◽  
Yuan Zhang ◽  
...  

6019 Background: Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling. Our previous single-arm phase 2 ALTN/MTC trial (NCT01874873) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic medullary thyroid carcinoma (MTC). Here we report results of the phase IIB trial (ALTER01031, NCT02586350) of anlotinib for locally advanced or metastatic MTC with a larger samples. Methods: Between September 2015 and September 2018, 91 patients were enrolled in China. Eligible patients have diagnosed as phase IV MTC with relapsed and measurable disease and without antiangiogenetic target therapy. The patients were randomly assigned in a 2:1 ratio to receive anlotinib or a matched placebo (12 mg QD from day 1 to 14 of a 21-day cycle). Patients who have been diagnosed with disease progression by the Independent Imaging Committee could be unblinded and crossed to the treatment group if the patient previous treated by placebo. The primary endpoint was progression-free survival (PFS). Results: 91 patients were randomized 62 to anlotinib arm and 29 to placebo arm. Until the data cutoff date (1 Feb 2019), median PFS was 20.67 months (95%CI, 14.03-34.63) in anlotinib arm vs 11.07 (95%CI, 5.82-14.32) months in placebo arm (HR 0.53, p = 0.0289). The OS data were not sufficiently mature for analysis. Considerable improvement in ORR was observed over the two arms (48.39% vs 3.45%, p < 0.0001). The adverse events (AEs) were 100% in anlotinib arm and 89.66% in placebo arm. The most common AEs in anlotinib arm were hand-foot syndrome, hypertension, hypertriglyceridemia and diarrhea. Conclusion: ALTER01031 met its primary endpoint of PFS shows that anlotinib treatment is effective and well tolerated. The safety profile was consistent and no new adverse events were identified. These data potentially extend the role of anlotinib monotherapy as a new therapy strategy for MTC patients. Clinical trial information: NCT02586350.



2006 ◽  
Vol 13 (2) ◽  
pp. 427-453 ◽  
Author(s):  
M Niedziela

According to the literature thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. A careful work-up, comprising the patient’s history, clinical examination, laboratory tests, thyroid ultrasound, scintigraphy, fine-needle aspiration biopsy (FNAB) and molecular studies, is mandatory to improve the preoperative diagnosis. The differential diagnosis should also include benign thyroid conditions such as: (i) congenital hypothyroidism due to dyshormonogenesis or ectopy, (ii) thyroid hemiagenesis, (iii) thyroglossal duct cyst, (iv) simple goiter, (v) cystic lesion, (vi) nodular hyperplasia, (vii) follicular adenoma, (viii) Graves’ disease and (ix) Hashimoto thyroiditis, all of which can predispose to the development of thyroid nodules. The majority of thyroid carcinomas derive from the follicular cell (papillary, follicular, insular and undifferentiated (or anaplastic) thyroid carcinoma), whereas medullary thyroid carcinoma derives from calcitonin-producing cells. Inherited forms of thyroid cancer may occur, especially in relation to medullary thyroid carcinoma. FNAB is a critical factor in establishing the preoperative diagnosis. However, we should keep in mind the fact that a conventional cytological evaluation can miss the neoplastic nature of a lesion and the employment of immunocytochemical and molecular studies of aspirates from FNAB can give us a more precise diagnosis of neoplasia in thyroid nodules once they are detected.



2019 ◽  
Vol 105 (6) ◽  
pp. NP28-NP31
Author(s):  
Marco Siano ◽  
Salvatore Alfieri ◽  
Roberta Granata ◽  
Giuseppina Calareso ◽  
Ester Orlandi ◽  
...  

Purpose: Two tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib, have been approved for recurrent/metastatic (R/M) medullary thyroid carcinoma (MTC). To date, it is still debated when and which TKI has to be started in R/M MTC patients. This is due to 1) TKI-related toxicity burden, 2) no overall survival benefit for either TKI, and 3) progression-free survival improvement in MTC subgroups ( RETM918T and RAS mutations) treated with cabozantinib. Herein, we present a case of R/M MTC with a discordant disease behavior because of spontaneous regression of some parenchymal sites along with progression of bone metastases, putting into the question the best timing for starting TKIs in R/M MTC. Methods: We report a 46-year-old man with relapse (lymph nodes in the neck and mediastinum) after curative treatment (total thyroidectomy plus central compartment and right neck dissection) for a locally advanced MTC with only somatic RETM918T mutation. Considering the low tumor burden, absence of symptoms, as well as the potential TKI-related side effects, we decided not to start systemic therapy when metastases first appeared. Results: Some lymph nodes spontaneously regressed, while new symptomatic bone lesions appeared with need for palliative radiotherapy. In total, first-line systemic therapy (cabozantinib) was started after 2 years since first distant metastases appearance. Conclusions: Radiologic progression of disease alone seems not to be adequate for MTC patients’ selection to be treated. The progression rate, the tumor burden, and the site of disease should also be taken into account for the clinical decision process.



Author(s):  
Andreas Kiriakopoulos ◽  
Anastasia Dimopoulou ◽  
Constantinos Nastos ◽  
Dimitra Dimopoulou ◽  
Konstantina Dimopoulou ◽  
...  

Abstract Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.



1998 ◽  
Vol 43 (2) ◽  
pp. 101-106 ◽  
Author(s):  
Syuya Shirahama ◽  
K. Ogura ◽  
Hiroshi Takami ◽  
Kunihiko Ito ◽  
Tohichi Tohsen ◽  
...  


Oncogene ◽  
1997 ◽  
Vol 14 (25) ◽  
pp. 3103-3106 ◽  
Author(s):  
Yutaka Kitamura ◽  
Paul J Goodfellow ◽  
Kazuo Shimizu ◽  
Mistuji Nagahama ◽  
Kunihiko Ito ◽  
...  




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