尿路上皮癌的免疫治療的最新進展

10.6666/ClinMed.201802_81(2).0020

顏厥全

免疫檢查哨(immune checkpoint) ； 計畫性死亡分子第一型(programmed cell death 1) ； 尿路上皮癌(urothelial carcinoma)

臨床醫學月刊

81卷2期（2018 / 02 / 23）

106 - 109

繁體中文

尿路上皮癌(urothelial carcinoma, UC，以前稱為移行細胞癌)是膀胱、輸尿管和腎盂癌最常見的組織學型態。對於不能手術的局部晚期或轉移的患者，多年來主要治療方法是以順鉑(cisplatin)為主的第一線化療處方，但效果有限且毒性不小。對腎功能不好，無法使用順鉑的病人，若改以卡鉑(carboplatin)治療，成績更差。而對經第一線治療失敗的病人，目前並無理想的後線藥物。免疫療法在膀胱癌的治療上已有悠久的歷史。早在1970年代就知道將卡介苗(Bacillus- Calmette Guerin, BCG)灌注在膀胱中可誘發免疫反應，有效控制非肌肉浸潤性膀胱癌患者。近年來，免疫療法在癌症治療上得到很大的突破。其中以對抗program cell death 1(PD-1)及PD-1 ligand 1(PD-L1)單株抗體最為成功。此類藥物可抑制腫瘤細胞與T細胞的免疫檢查哨(immune checkpoint)作用，解除免疫容忍(immune tolerance)現象，重新活化T細胞的抑癌能力。本文將針對最近此類免疫檢查哨抑制劑，對UC治療的臨床試驗，做一簡介。

1. Balar, AV,Galsky, MD,Rosenberg, JE(2017).Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.Lancet,389,67-76.
2. Bellmunt, J,de Wit, R,Vaughn, DJ(2017).Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.N Engl J Med,376,1015-1026.
3. Cancer Genome Atlas Research N(2014).Comprehensive molecular characterization of urothelial bladder carcinoma.Nature,507,315-322.
4. Coe, JE,Feldman, JD(1966).Extracutaneous delayed hypersensitivity, particularly in the guinea-pig bladder.Immunology,10,127-136.
5. De Santis, M,Bellmunt, J,Mead, G(2009).Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986.J Clin Oncol,27,5634-5639.
6. Hung, CF,Yang, CK,Ou, YC(2016).Urologic cancer in Taiwan.Jpn J Clin Oncol,46,605-609.
7. Lamm, DL,Thor, DE,Harris, SC(1980).Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer.J Urol,124,38-40.
8. Morales, A,Eidinger, D,Bruce, AW(1976).Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors.J Urol,116,180-183.
9. Postow, MA,Callahan, MK,Wolchok, JD(2015).Immune Checkpoint Blockade in Cancer Therapy.J Clin Oncol,33,1974-1982.
10. Rosenberg, JE,Hoffman-Censits, J,Powles, T(2016).Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.Lancet,387,1909-1920.
11. Sharma, P,Retz, M,Siefker-Radtke, A(2017).Nivolumab in metastatic urothelial carcinoma after platinum therapy(CheckMate 275): a multicentre, single-arm, phase 2 trial.Lancet Oncol,18,312-322.
12. Sonpavde, G,Sternberg, CN,Rosenberg, JE(2010).Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of The urothelium.Lancet Oncol,11,861-870.
13. Sternberg, CN,de Mulder, P,Schornagel, JH(2006).Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.Eur J Cancer,42,50-54.
14. von der Maase, H,Sengelov, L,Roberts, JT(2005).Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer.J Clin Oncol,23,4602-4608.

1. (2024)。面對一位未被告知罹患膀胱癌末期病人之照護經驗。彰化護理，31(2)，107-117。