术前化疗后乳腺癌的卡培他滨辅助治疗 - NEJM医学前沿
提示: 手机请竖屏浏览!

术前化疗后乳腺癌的卡培他滨辅助治疗
Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy


Norikazu Masuda ... 肿瘤 • 2017.06.01
相关阅读
• 铂类化疗可否用于BRCA相关三阴性乳腺癌 • 卡培他滨用于术后残留乳腺癌的治疗 • 贝伐单抗联合新辅助化疗治疗乳腺癌

摘要


背景

接受针对人表皮生长因子受体2(HER2)阴性乳腺癌的新辅助化疗后,仍有残余浸润性癌的患者预后不良。辅助化疗在这些患者中的益处尚不清楚。

 

方法

我们将接受新辅助化疗(包括蒽环类抗生素、紫杉烷或两者兼有)后仍有HER2阴性残余浸润性乳腺癌的910例患者随机分组,分别使其接受联合或不联合(对照)卡培他滨的标准术后治疗。主要终点是无病生存期。次要终点包括总生存期。

 

结果

预先设定的中期分析结果达到了主要终点,所以本试验被提前终止。最终分析显示卡培他滨组的无病生存期比对照组长(5年时仍存活,并且没有癌症再发或患第二种癌的患者比例,74.1%对67.6%;再发、患第二种癌或死亡的风险比为0.70;95%置信区间[CI],0.53~0.92;P=0.01)。卡培他滨组的总生存期比对照组长(5年时仍存活的患者比例,89.2%对83.5%;死亡风险比为0.59;95% CI,0.39~0.90;P=0.01)。在三阴性乳腺癌患者中,卡培他滨组的无病生存率为69.8%,而对照组为56.1%(再发、患第二种癌或死亡的风险比为0.58;95% CI,0.39~0.87);而总生存率为78.8%对70.3%(死亡风险比为0.52;95% CI,0.30~0.90)。卡培他滨的最常见不良反应手足综合征发生于卡培他滨组73.4%的患者。

 

结论

接受包括蒽环类抗生素、紫杉烷或两者兼有的标准新辅助化疗后,在病理学检查中有残余浸润性癌的HER2阴性乳腺癌患者中,加用卡培他滨辅助治疗是安全的,并且对于延长无病生存期和总生存期有效(由高级临床研究机构[Advanced Clinical Research Organization]和日本乳腺癌研究组[Japan Breast Cancer Research Group]资助;CREATE-X UMIN临床试验注册号,UMIN000000843)。





作者信息

Norikazu Masuda, M.D., Ph.D., Soo-Jung Lee, M.D., Ph.D., Shoichiro Ohtani, M.D., Ph.D., Young-Hyuck Im, M.D., Ph.D., Eun-Sook Lee, M.D., Ph.D., Isao Yokota, Ph.D., Katsumasa Kuroi, M.D., Ph.D., Seock-Ah Im, M.D., Ph.D., Byeong-Woo Park, M.D., Ph.D., Sung-Bae Kim, M.D., Ph.D., Yasuhiro Yanagita, M.D., Ph.D., Shinji Ohno, M.D., Ph.D., Shintaro Takao, M.D., Ph.D., Kenjiro Aogi, M.D., Ph.D., Hiroji Iwata, M.D., Ph.D., Joon Jeong, M.D., Ph.D., Aeree Kim, M.D., Ph.D., Kyong-Hwa Park, M.D., Ph.D., Hironobu Sasano, M.D., Ph.D., Yasuo Ohashi, Ph.D., and Masakazu Toi, M.D., Ph.D.
From the National Hospital Organization Osaka National Hospital, Osaka (N.M.), Hiroshima City Hiroshima Citizens Hospital, Hiroshima (S. Ohtani), Kyoto Prefectural University of Medicine (I.Y.), and Graduate School of Medicine, Kyoto University (M.T.), Kyoto, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital (K.K.), and Chuo University (Y.O.), Tokyo, Gunma Prefectural Cancer Center, Ota (Y.Y.), National Hospital Organization Kyushu Cancer Center, Fukuoka (S. Ohno), Hyogo Cancer Center, Akashi (S.T.), National Hospital Organization Shikoku Cancer Center, Matsuyama (K.A.), Aichi Cancer Center Hospital, Nagoya (H.I.), and Tohoku University, Sendai (H.S.) — all in Japan; and Yeungnam University Hospital, Daegu (S.-J.L.), Samsung Medical Center, Sungkyunkwan University School of Medicine (Y.-H.I.), Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine (S.-A.I.), Severance Hospital (B.-W.P.) and Gangnam Severance Hospital (J.J.), Yonsei University College of Medicine, Asan Medical Center, University of Ulsan College of Medicine (S.-B.K.), Korea University Guro Hospital (A.K.), and Korea University Anam Hospital (K.-H.P.), Seoul, and National Cancer Center, Goyang-si (E.-S.L.) — all in South Korea. Address reprint requests to Dr. Toi at the Breast Cancer Unit, Kyoto University Hospital, Breast Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan, or at toi@kuhp.kyoto-u.ac.jp. A complete list of the investigators in the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164-172

2. Kuroi K, Toi M, Ohno S, et al. Prognostic significance of subtype and pathologic response in operable breast cancer; a pooled analysis of prospective neoadjuvant studies of JBCRG. Breast Cancer 2015;22:486-495

3. National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN guidelines): breast cancer version 2. 2016 (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf).

4. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies — improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015;26:1533-1546

5. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696-2704

6. Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012;379:315-321

7. Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol 2014;15:1389-1396

8. Martín M, Ruiz Simón A, Ruiz Borrego M, et al. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol 2015;33:3788-3795

9. Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, et al. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol 2012;30:11-18

10. Blum JL, Jones SE, Buzdar AU, et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999;17:485-493

11. Miles D, von Minckwitz G, Seidman AD. Combination versus sequential single-agent therapy in metastatic breast cancer. Oncologist 2002;7:Suppl 6:13-19

12. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355:2733-2743

13. Pallis AG, Boukovinas I, Ardavanis A, et al. A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol 2012;23:1164-1169

14. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2006;24:2019-2027

15. Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC cancer staging manual. 7th ed. New York: Springer, 2011.

16. Kuroi K, Toi M, Tsuda H, Kurosumi M, Akiyama F. Issues in the assessment of the pathologic effect of primary systemic therapy for breast cancer. Breast Cancer 2006;13:38-48

17. National Cancer Institute. Common terminology criteria for adverse events (CTCAE) v3.0. August 9, 2006 (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf).

18. Morimoto T, Ogawa M, Orita K, et al. Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan. Eur J Cancer 1996;32A:235-242

19. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;351:1451-1467

20. Taguchi T, Terasawa T, Abe O, Yoshida Y, Tominaga T, Ogawa N. A comparative study of 5′-DFUR and tegafur in recurrent breast cancer Gan To Kagaku Ryoho 1985;12:2052-2060. (In Japanese.)

21. Iwata H, Nakamura S, Toi M, et al. Interim analysis of a phase II trial of cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by docetaxel as preoperative chemotherapy for early stage breast carcinoma. Breast Cancer 2005;12:99-103

22. Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics 1982;38:163-170

23. DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med 1994;13:1341-1352

24. Toi M, Atiqur Rahman M, Bando H, Chow LW. Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment. Lancet Oncol 2005;6:158-166

25. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-1684

26. Sparano JA, Zhao F, Martino S, et al. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol 2015;33:2353-2360

27. Moebus V, Jackisch C, Lueck HJ, et al. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol 2010;28:2874-2880

28. Ellis GK, Barlow WE, Gralow JR, et al. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol 2011;29:1014-1021

29. Leichman CG. Schedule dependency of 5-fluorouracil. Oncology (Williston Park) 1999;13:Suppl 3:26-32

30. Bear HD, Tang G, Rastogi P, et al. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol 2015;16:1037-1048

31. von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol 2010;28:2015-2023

32. Ohno S, Chow LW, Sato N, et al. Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil–epirubicin–cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy. Breast Cancer Res Treat 2013;142:69-80

33. O’Shaughnessy J, Koeppen H, Xiao Y, et al. Patients with slowly proliferative early breast cancer have low five-year recurrence rates in a phase III adjuvant trial of capecitabine. Clin Cancer Res 2015;21:4305-4311

34. Lluch A, Gomez H, Ruiz-Borrego M, et al. First safety data from a randomised phase III (CIBOMA 2004- 01/GEICAM 2003-11) trial assessing adjuvant capecitabine maintenance therapy after standard chemotherapy for triple-negative early breast cancer. Presented at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8–12, 2010. abstract.

35. Mackean M, Planting A, Twelves C, et al. Phase I and pharmacologic study of intermittent twice-daily oral therapy with capecitabine in patients with advanced and/or metastatic cancer. J Clin Oncol 1998;16:2977-2985

36. Ma Y, Tang L, Wang HX, Xu YC, Ma Y, Zhang FC. Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity. J Clin Pharm Ther 2012;37:266-275

37. Haller DG, Cassidy J, Clarke SJ, et al. Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol 2008;26:2118-2123


服务条款 | 隐私政策 | 联系我们