- 著者
- Yasuhiro Ito Shinichi Suzuki Ken-ichi Ito Tsuneo Imai Takahiro Okamoto Hiroya Kitano Iwao Sugitani Kiminori Sugino Hidemitsu Tsutsui Hisato Hara Akira Yoshida Kazuo Shimizu
- 出版者
- (社)日本内分泌学会
- 雑誌
- Endocrine Journal (ISSN:09188959)
- 巻号頁・発行日
- pp.EJ16-0064, (Released:2016-05-20)
- 被引用文献数
- 23
Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients’ quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.
- 著者
- Daishu Miura Kimiyasu Yoneyama Yoshiaki Furuhata Kazuo Shimizu
- 出版者
- 日本医科大学医学会
- 雑誌
- Journal of Nippon Medical School (ISSN:13454676)
- 巻号頁・発行日
- vol.81, no.4, pp.211-220, 2014 (Released:2014-09-03)
- 参考文献数
- 26
- 被引用文献数
- 5 18
Introduction: An important mechanism by which trastuzumab inhibits the growth of human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is the activation of a host tumor response via antibody-dependent cell-mediated cytotoxicity (ADCC). Although paclitaxel has a synergistic effect in combination with trastuzumab, whether ADCC is enhanced by paclitaxel is not known. In the present study we examined whether adding paclitaxel to trastuzumab enhances ADCC and also investigated the kinetics of effector cells in ADCC. Materials and Methods: The subjects were 20 patients with HER2-positive breast cancer: 9 received the combination of trastuzumab (4 mg/kg as a loading dose and 2 mg/kg weekly) and paclitaxel (80 mg/m2 weekly) and 19 received monotherapy with trastuzumab. In blood samples (mononuclear cells) obtained before and 10 minutes after administration of chemotherapy, ADCC and the number of effector cells, including natural killer (NK) cells, monocytes, and CD64+ cells, were compared in each case. The ADCC was analyzed with a 51Cr releasing assay using the SK-BR-3 cell line, and the fractions of NK cells (both CD16+ [FcγRIII] and CD56+) and CD64+ (FcγRI) cells were analyzed with flow cytometry. Results: The mean ADCC level increased 20% after trastuzumab monotherapy and 126% (p<0.05) after combination therapy with trastuzumab and paclitaxel. All 9 patients receiving combination therapy had increased ADCC levels. The number of NK cells increased 51% after trastuzumab monotherapy and 112% (p<0.05) after combination therapy. No significant changes were found in monocytes (39% increase) or CD64+ cells (53% increase) after trastuzumab monotherapy, but monocytes decreased 40% (p<0.05) and CD64+ cells decreased 24% after combination therapy. Conclusions: Adding paclitaxel to trastuzumab significantly enhances ADCC, with levels twice as great as with trastuzumab monotherapy, through a rapid recruitment of NK cells. This finding suggests that the combination of trastuzumab and paclitaxel has a stronger-than-expected synergistic effect in HER2-positive breast cancer.