癌症患者使用依维莫司会增加高血糖风险的系统评价

doi:10.5246/jcps.2015.05.042

摘要/Abstract

摘要：

依维莫司是一种口服的雷帕霉素抑制剂, 已经被批准用于多种实体瘤的治疗, 但是部分患者在使用依维莫司后出现了高血糖的不良反应。在这篇系统评价中, 我们将评估使用依维莫司的患者高血糖的发生率及相对风险。全面检索Cochrane Library, PubMed, EMBASE数据库及国际顶尖会议(AACR, ASCO, 和ESMO)的会议摘要, 纳入2014年11月之前发表的随机对照试验(RCT)。总共有来自8个RCT的3377名患者(依维莫司组: 1971, 对照组: 1406)被纳入系统评价。在依维莫司组, 所有级别高血糖的发生率为20.0% (95% CI: 11.0%–29.0%), 高级别(3–4级)高血糖的发生率为6.0% (95% CI: 3.0%–8.0%)。依维莫司组所有级别高血糖的发生率是对照组的2.94倍(95% CI: 2.34–3.70), 依维莫司组高级别高血糖的发生率是对照组的4.66倍(95% CI: 2.75–7.89)。依维莫司可显著增加高血糖的发生风险, 且风险与肿瘤类型和依维莫司的剂量相关。

关键词: 依维莫司, 高血糖, 肿瘤类型, 剂量, 系统评价

Abstract:

Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-analysis, we aimed to evaluate the incidence and risk of hyperglycemia in patients with cancer who received everolimus. We searched the medical literature, as index in the Cochrane Library, PubMed, EMBASE, and abstracts from the top scientific meetings (AACR, ASCO, and ESMO). Our meta-analysis included the randomly controlled trials published before November 2014. We calculated overall incidence, relative risk (RR) and 95% confidence intervals (CI) using fixed-effects or random-effects models, depending on the heterogeneity among the trials. A total of 3377 patients (everolimus: 1971; control: 1406) from 8 randomized clinical trials were included in the meta-analysis. In the everolimus groups, the incidence of all grades of hyperglycemia was 20.0% (95% CI: 11.0%–29.0%), while the incidence of high-grade hyperglycemia was 6.0% (95% CI: 3.0%–8.0%). Patients treated with everolimus had an increased risk of hyperglycemia as compared with that of controls (all-grade RR: 2.94, 95% CI: 2.34–3.70; high-grade RR: 4.66, 95% CI: 2.75–7.89). Everolimus significantly increased the risk of hyperglycemia. This risk may depend on the tumor type and the everolimus dosage.

Key words: Everolimus, Hyperglycemia, Tumor type, Dosage, Meta-analysis

中图分类号:

R954

Supporting:

郭子寒, 焦园园, 易占苗, 李然, 张艳华. 癌症患者使用依维莫司会增加高血糖风险的系统评价[J]. 中国药学(英文版), 2015, 24(5): 326-335.

Zihan Guo, Yuanyuan Jiao, Zhanmiao Yi, Ran Li, Yanhua Zhang. Increased risk of hyperglycemia associated with the use of everolimus in patients with cancer: a systematic review and meta-analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(5): 326-335.

参考文献

[1] Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Nat. Rev. Drug Discov. 2009, 8, 627-644 .

[2] Wullschleger, S.; Loewith, R.; Hall, M.N. Cell. 2006, 124, 471-684.

[3] Guertin, D.A.; Sabatini, D.M. Cancer Cell. , 12, 9-22.2007

[4] Aapro, M.; Andre, F.; Blackwel, l.K. Ann. Oncol. 2014, 25, 763-673.

[5] Ravaud, A.; Urva, S.R.; Grosch, K. Eur. J. Cancer. 2014, 50, 486-495.

[6] Iacovelli, R.; Palazzo, A.; Mezi, S. Acta Oncol. 2012, 51, 873-879.

[7] Funakoshi, T.; Latif, A.; Galsky, M.D. Crit. Rev. Oncol. Hematol. 2013, 88, 30-41.

[8] Paplomata, E.; Zelnak, A.; O'Regan, R. Breast Cancer Res. Treat. 2013, 140, 453-462.

[9] Motzer, R.J., Escudier, B.; Oudard, S. Cancer. 2010, 116, 4256-4265.

[10] Ellard, S.L.; Clemons, M.; Gelmon, K.A. . 2009, 27, 4536-4541.Clin. Oncol.J

[11] Mitri, J.; Castillo, J.; Pittas, A.G. Diabetes Care. 2008, 31, 2391-2397.

[12] Fang, H.; Yao, B.; Yan, Y. Diabetes Technol. Ther. 2013, 15, 914-922.

[13] El-Serag, H.B.; Hampel, H.; Javadi, F. Clin. Gastroenterol. Hepatol. 2006, 4, 369-480.

[14] Liao, S.; Li, J.; Wei, W. Asian Pac. J. Cancer Prev. 2011, 12, 1061-1065.

[15] Huxley, R.; Ansary-Moghaddam, A.; Berrington, D.G.A. Br. J. Cancer. 2005, 92, 2076-2083.

[16] Chari, S.T.; Leibson, C.L.; Rabe K.G. Gastroenterology. 2005, 129, 504-511.

[17] Mills, K.T.; Bellows, C.F.; Hoffman, A.E. Dis. Colon. Rectum. 2013, 56, 1304-1319.

[18] Larsson, S.C.; Giovannucci, E.; Wolk, A. Diabetes Care. 2005, 28, 1805-1807.

[19] Michels, K.B.; Solomon, C.G.; Hu, F.B. Diabetes Care. 2003, 26, 1752-1758.

[20] Noto, H.; Goto, A.; Tsujimoto, T.; Noda, M. PLoS One. 2012, 7, e33411.

[21] Evans, J.M.; Donnelly, L.A.; Emslie-Smith, A.M. BMJ. 2005, 330, 1304-1305.

[22] Zoncu, R.; Efeyan, A.; Sabatini, D.M. Nat. Rev. Mol. Cell Biol. 2011, 12, 21-35.

[23] Yamanaka, K.; Petrulionis, M.; Lin, S. Cancer Med. 2013, 2, 862-871.

[24] Sivendran, S.; Agarwal, N.; Gartrell, B. Cancer Treat Rev. 2014, 40, 190-196.

[25] Maass, N.; Harbeck, N.; Mundhenke, C. J. Cancer Res. Clin. Oncol. 2013, 139, 2047-2056.

[26] Andre, F.; O'Regan, R.; Ozguroglu, M. Lancet Oncol. 2014, 15, 580-591.

[27] Zhu, A.X.; Kudo, M.; Assenat, E. JAMA. 2014, 312, 57.

[28] Higgins, J.P.T.G.S. Cochrane. This article can be found online at http://handbook.cochrane.org

[29] DerSimonian, R.; Laird, N. Control Clin. Trials. 1986, 7, 177-188.

[30] Higgins, J.P.T.; Thompson, S.G. Stat. Med. 2002, 21, 1539-1558.

[31] Begg, C.B.; Mazumdar, M. Biometrics. 1994, 50, 1088-1101.

[32] Egger, M.; Davey, S.G.; Schneider, M. BMJ. 1997, 315, 629-634.

[33] NCI. This article can be found online at http://ctep. cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

[34] Pavel, M.E.; Hainsworth, J.D.; Baudin, E. Lancet. 2011, 378, 2005-2012.

[35] Yao, J.C.; de Vries, E.G.E.; Tomassetti, P. N Engl. J. Med. 2011, 364, 514-523.

[36] Baselga, J.; Campone, M.; Piccart, M. N Engl. J. Med. 2012, 366, 520-529.

[37] Baselga, J.; Semiglazov, V.; van Dam, P. J. Clin. Oncol. 2009, 27, 2630-2637.

[38] Shiah, H.S.; Chen, C.Y.; Dai, C.Y. Aliment. Pharmacol. Ther. 2013, 37, 62-73.

[39] FDA. This article can be found online at http://www. pharma.us.novartis.com/product/pi/pdf/afinitor.pdf

[40] Amato, R.; Stepankiw, M. Expert Opin. Pharmacother. 2013, 14, 1229-1240.

[41] Zoncu, R.; Efeyan, A.; Sabatini, D.M. Nat. Rev. Mol. Cell Biol. 2011, 12, 21-35.

[42] Laplante, M.; Sabatini, D.M. Cell. 2012, 149, 274-293.

[43] Fraenkel, M.; Ketzinel-Gilad, M.; Ariav, Y. Diabetes. 2008, 57, 945-957.

[44] Franz, D.N.; Belousova, E.; Sparagana, S. Lancet. 2013, 381, 125-132.

[45] Bissler, J.J.; Kingswood, J.C.; Radzikowska, E. Lancet. 2013, 381, 817-824.

[46] Ohtsu, A.; Ajani, J.A.; Bai, Y.X. J. Clin. Oncol. 2013, 31, 3935-3943.

[47] Bachelot, T.; Bourgier, C.; Cropet, C. J. Clin. Oncol. 2012, 30, 2718-2724.

[48] von Minckwitz, G.; Eidtmann, H.; Loibl, S. Ann. Oncol. 2011, 22, 301-306.