Cargando…

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

Background: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approv...

Descripción completa

Detalles Bibliográficos
Autores principales: Ito, Yasuhiro, Onoda, Naoyoshi, Ito, Ken-ichi, Sugitani, Iwao, Takahashi, Shunji, Yamaguchi, Iku, Kabu, Koki, Tsukada, Katsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646744/
https://www.ncbi.nlm.nih.gov/pubmed/28635560
http://dx.doi.org/10.1089/thy.2016.0621
_version_ 1783272138344497152
author Ito, Yasuhiro
Onoda, Naoyoshi
Ito, Ken-ichi
Sugitani, Iwao
Takahashi, Shunji
Yamaguchi, Iku
Kabu, Koki
Tsukada, Katsuya
author_facet Ito, Yasuhiro
Onoda, Naoyoshi
Ito, Ken-ichi
Sugitani, Iwao
Takahashi, Shunji
Yamaguchi, Iku
Kabu, Koki
Tsukada, Katsuya
author_sort Ito, Yasuhiro
collection PubMed
description Background: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Methods: Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. Results: A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7–5.6], and median OS was 5.0 months [confidence interval 0.7–5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. Conclusions: The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.
format Online
Article
Text
id pubmed-5646744
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Mary Ann Liebert, Inc.
record_format MEDLINE/PubMed
spelling pubmed-56467442017-10-27 Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma Ito, Yasuhiro Onoda, Naoyoshi Ito, Ken-ichi Sugitani, Iwao Takahashi, Shunji Yamaguchi, Iku Kabu, Koki Tsukada, Katsuya Thyroid Thyroid Cancer and Nodules Background: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Methods: Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. Results: A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7–5.6], and median OS was 5.0 months [confidence interval 0.7–5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. Conclusions: The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC. Mary Ann Liebert, Inc. 2017-09-01 2017-09-01 /pmc/articles/PMC5646744/ /pubmed/28635560 http://dx.doi.org/10.1089/thy.2016.0621 Text en © Yasuhiro Ito et al. 2017; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Thyroid Cancer and Nodules
Ito, Yasuhiro
Onoda, Naoyoshi
Ito, Ken-ichi
Sugitani, Iwao
Takahashi, Shunji
Yamaguchi, Iku
Kabu, Koki
Tsukada, Katsuya
Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title_full Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title_fullStr Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title_full_unstemmed Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title_short Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
title_sort sorafenib in japanese patients with locally advanced or metastatic medullary thyroid carcinoma and anaplastic thyroid carcinoma
topic Thyroid Cancer and Nodules
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646744/
https://www.ncbi.nlm.nih.gov/pubmed/28635560
http://dx.doi.org/10.1089/thy.2016.0621
work_keys_str_mv AT itoyasuhiro sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT onodanaoyoshi sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT itokenichi sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT sugitaniiwao sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT takahashishunji sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT yamaguchiiku sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT kabukoki sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma
AT tsukadakatsuya sorafenibinjapanesepatientswithlocallyadvancedormetastaticmedullarythyroidcarcinomaandanaplasticthyroidcarcinoma