紫杉醇剂量密集化疗在原发性上皮性卵巢癌中疗效与安全性Meta分析
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摘要
目的:系统评价紫杉醇剂量密集化疗在原发性上皮性卵巢癌中的疗效与安全性。方法:检索Cochrane Library、Pubmed、Embase、Medline、中国知网(CNKI)、维普(VIP)、万方、中国生物医学文献数据库(CBM)等数据库,并手工检索会议摘要及相关参考文献,应用Cochrane偏倚风险评估工具5.1版进行偏倚风险评价,RevMan 5.3行Meta分析。结果:纳入11项RCT研究共4 590例患者,Meta分析结果显示紫杉醇剂量密集化疗与三周化疗方案无进展生存期(progressio free survival,PFS)(HR=0.89,95%CI 0.77～1.04,P=0.14)、整体生存率(overall survival,OS)(HR=0.94,95%CI 0.82～1.07,P=0.35)差异无统计学意义,同样未提升患者生存率、客观缓解率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)(P>0.05),但降低了患者疾病进展(progressive disease,PD)发生率(OR=0.54, 95%CI 0.29～0.99,P=0.05);亚组分析显示剂量密集化疗延长老年患者(≥60岁)和FIGO分期III～IV期患者的PFS(P<0.05);安全性分析显示,剂量密集化疗增加3级以上贫血(OR=2.35,95%CI 1.38～3.99,P=0.002)、腹泻(OR=1.74,95%CI 1.01～2.74,P=0.02)发生率,其他3级以上不良反应均未见统计学差异(P>0.05)。结论:剂量密集化疗未改善原发上皮性卵巢癌患者PFS、OS、ORR、DCR和生存率,并增加了患者3级以上贫血、腹泻发生率,但延长老年及晚期患者PFS,降低PD发生率。
Objective: To systematically evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer. Methods: Conference-related abstracts and relevant articles were searched and manually retrieved from Cochrane Library, Pubmed, Embase, Medline, CINK, VIP, Wanfang, and CBM databases. We applied the Cochrane bias risk assessment tool(version 5.1) to evaluate the risk of bias, and meta-analysis was conducted by RevMan 5.3 software. Results: A total of 11 randomized control trials(4,590 patients) were included. Meta-analysis showed that there was no statistically significant difference between the experiment group and the control group in progression free survival(PFS)(HR=0.89,95% CI 0.77～1.04,P=0.14) and overall survival(OS)(HR=0.94,95% CI 0.82～1.07,P=0.35). Patient survival rate, objective response rate(ORR) and disease control rate(DCR) were not improved(P>0.05), while the incidence of progressive disease(PD) reduced(OR=0.54 95% CI 0.29～0.99,P=0.05). Subgroup analysis showed that dose-dense chemotherapy prolonged PFS in elderly patients(≥60 years) and FIGO stage III-IV patients(P<0.05). Safety analysis showed that dose-dense chemotherapy increased the incidence of anemia(OR=2.35, 95% CI 1.38～3.99,P=0.002) and diarrhea(OR=1.74,95% CI 1.01～2.74,P=0.02) above grade 3. There were no statistically significant differences in other adverse reactions above grade 3(P>0.05). Conclusion: Dose-dense chemotherapy does not improve PFS, OS, ORR, DCR and survival rate in patients with primary epithelial ovarian cancer, and may increase incidence of anemia, diarrhea above grade 3. However, it may prolong PFS in elderly and advanced patients, and reduce the incidence of PD.
Objective: To systematically evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer. Methods: Conference-related abstracts and relevant articles were searched and manually retrieved from Cochrane Library, Pubmed, Embase, Medline, CINK, VIP, Wanfang, and CBM databases. We applied the Cochrane bias risk assessment tool(version 5.1) to evaluate the risk of bias, and meta-analysis was conducted by RevMan 5.3 software. Results: A total of 11 randomized control trials(4,590 patients) were included. Meta-analysis showed that there was no statistically significant difference between the experiment group and the control group in progression free survival(PFS)(HR=0.89,95% CI 0.77～1.04,P=0.14) and overall survival(OS)(HR=0.94,95% CI 0.82～1.07,P=0.35). Patient survival rate, objective response rate(ORR) and disease control rate(DCR) were not improved(P>0.05), while the incidence of progressive disease(PD) reduced(OR=0.54 95% CI 0.29～0.99,P=0.05). Subgroup analysis showed that dose-dense chemotherapy prolonged PFS in elderly patients(≥60 years) and FIGO stage III-IV patients(P<0.05). Safety analysis showed that dose-dense chemotherapy increased the incidence of anemia(OR=2.35, 95% CI 1.38～3.99,P=0.002) and diarrhea(OR=1.74,95% CI 1.01～2.74,P=0.02) above grade 3. There were no statistically significant differences in other adverse reactions above grade 3(P>0.05). Conclusion: Dose-dense chemotherapy does not improve PFS, OS, ORR, DCR and survival rate in patients with primary epithelial ovarian cancer, and may increase incidence of anemia, diarrhea above grade 3. However, it may prolong PFS in elderly and advanced patients, and reduce the incidence of PD.
引文
[1] Henderson JT, Webber EM, Sawaya GF. Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force[J]. JAMA, 2018, 319(6): 595-606.
[2] Stewart SL, Harewood R, Matz M, et al. Disparities in ovarian cancer survival in the United States (2001-2009): findings from the CONCORD-2 study[J]. Cancer, 2017, 123(S24):5100.
[3] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[4] Orr B, Edwards RP. Diagnosis and treatment of ovarian cancer[J]. Hematol Oncol Clin North Am, 2018, 32(6): 943-964.
[5] Norton L, Simon R. The Norton-Simon hypothesis revisited[J]. Cancer Treat Rep, 1986, 70(1): 163-169.
[6] Liu MC, Pitcher BN, Mardis ER, et al. PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)[J]. NPJ Breast Cancer, 2016, 2:15023.
[7] Zhu T, Liu CL, Zhang YF, et al. A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer[J]. Breast Cancer Res Treat, 2016, 156(1):117-124.
[8] Takabatake D, Kajiwara Y, Ohtani S, et al. The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese patients with breast cancer[J]. Breast cancer, 2018, 25(6):717-722.
[9] Zhou W, Chen S, Xu F. Survival benefit of pure dose-dense chemotherapy in breast cancer: a meta-analysis of randomized controlled trials[J]. World J Surg Oncol, 2018, 16(1): 144-152.
[10] Goldvaser H, Majeed H, Ribnikar D, et al. Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis[J]. Breast Cancer Res Treat, 2018, 169(3): 413-425.
[11] M?bus V, Jackisch C, Lück HJ, et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial[J]. Ann Oncol, 2018, 29(1):178-185.
[12] 梁江红, 冷小飞, 程萍, 等. 紫杉醇剂量密度方案化疗在上皮性卵巢癌应用的疗效及安全性meta分析[J].现代妇产科进展, 2015, 24(6): 416-420.
[13] 范淑英, 王健, 刘芸, 等. 紫杉醇联合卡铂周疗和三周疗法治疗卵巢癌的Meta分析[J]. 解放军医学杂志, 2016, 41(7): 589-597.
[14] Miller AB,Hongstraten B,Staquet M,et al. Reporting results of cancer treatment[J]. Cancer, 1981, 47(1): 207-214.
[15] National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Program. National Cancer Institute Common Toxicity Criteria, version 2.0. [EB/OL].https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm, /1999-4-30.
[16] Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8(1):16.
[17] Clamp AR, McNeish I, Dean A, et al. ICON8: a GCIG phase III randomised trial evaluating weekly dose-dense chemotherapy integration in firstline epithelial ovarian/fallopian tube/primary peritoneal carcinoma (EOC) treatment:results of primary progression free survival (PFS) analysis[C]. Ann Oncol (Meeting Abstracts), 2017, 28 (S5): v605–v649.
[18] Chan JK, Brady MF, Penson RT, et al. Weekly vs. every-3-Week paclitaxel and carboplatin for ovarian cancer[J]. N Engl J Med, 2016, 71(8):738-748.
[19] Du ZH, Ma XL. Dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin treatment for stage II-IV ovarian cancer patients[ J]. Bangladesh J Pharmacol, 2015, 10(3): 489-493.
[20] 贺凌云, 朱炜, 罗君玲, 等. 单周与3周紫杉醇联合卡铂方案治疗卵巢癌临床疗效分析[J]. 中国现代医药杂志, 2015,17(9):12-15.
[21] Pignata S,Scambia G,Katsaros D,et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet Oncol,2014, 15(4):396-405.
[22] Burg MEL, Onstenk W, Boere IA, et al. Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer[J]. Eur J Cancer, 2014, 50(15): 2592-2601.
[23] Katsumata N, Yasuda M, Isonishi S, et al. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial[J]. Lancet Oncol, 2013, 14(10):1020-1026.
[24] 陈为, 王善林, 周龙书, 等. 紫杉醇联合卡铂周疗和三周疗法治疗上皮性卵巢癌的疗效比较[J]. 中国现代医生, 2013, 51(17):37-39.
[25] 张冬梅, 闫玉兰, 王英, 等. 剂量密集化疗治疗晚期上皮性卵巢癌疗效观察[J]. 国际妇产科学杂志, 2013, 40(5):472-474.
[26] 刘云军, 何志江, 黄毅超, 等. 单周紫杉醇化疗方案在晚期卵巢癌的临床应用[J]. 中华全科医学, 2013, 11(8):1231-1232.
[27] 沈铿, 李孟达, 丰有吉, 等. 泰素周疗和三周疗法作为卵巢癌一线化疗的多中心对照研究[J]. 中华医学杂志, 2005, 85(30):2099-2103.
[28] Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review[J]. Cancer Biol Med, 2017, 14(1):9-32.
[29] National Comprehensive Cancer Network Guidelines Version 2.2018 Ovarian Cancer.[EB/OL].http://www.nccn.org.
[30] National Comprehensive Cancer Network Guidelines Version 3.2018 Breast Cancer. [EB/OL].http://www.nccn.org/patients.
[31] Loizzi V, Del Vecchio V, Crupano FM, et al. A phase II study: dose-dense carboplatin and paclitaxel as neoadjuvant chemotherapy in locally advanced cervical cancer[J]. J Chemother, 2018, 30(4): 247-252.
[32] Kogan L, Laskov I, Amajoud Z, et al. Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer[J]. Gynecol Oncol, 2017, 147(1): 30-35.
[33] Garcia CR, Slone SA, Morgan RM, et al. Dose-dense temozolomide for recurrent high-grade gliomas: a single-center retrospective study[J]. Med Oncol, 2018, 35(10):136-144.
[34] Zhu C, Liu J, Zhang J, et al. Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma[J]. Oncotarget, 2017, 8(41): 71117-71127.
[2] Stewart SL, Harewood R, Matz M, et al. Disparities in ovarian cancer survival in the United States (2001-2009): findings from the CONCORD-2 study[J]. Cancer, 2017, 123(S24):5100.
[3] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[4] Orr B, Edwards RP. Diagnosis and treatment of ovarian cancer[J]. Hematol Oncol Clin North Am, 2018, 32(6): 943-964.
[5] Norton L, Simon R. The Norton-Simon hypothesis revisited[J]. Cancer Treat Rep, 1986, 70(1): 163-169.
[6] Liu MC, Pitcher BN, Mardis ER, et al. PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)[J]. NPJ Breast Cancer, 2016, 2:15023.
[7] Zhu T, Liu CL, Zhang YF, et al. A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer[J]. Breast Cancer Res Treat, 2016, 156(1):117-124.
[8] Takabatake D, Kajiwara Y, Ohtani S, et al. The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese patients with breast cancer[J]. Breast cancer, 2018, 25(6):717-722.
[9] Zhou W, Chen S, Xu F. Survival benefit of pure dose-dense chemotherapy in breast cancer: a meta-analysis of randomized controlled trials[J]. World J Surg Oncol, 2018, 16(1): 144-152.
[10] Goldvaser H, Majeed H, Ribnikar D, et al. Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis[J]. Breast Cancer Res Treat, 2018, 169(3): 413-425.
[11] M?bus V, Jackisch C, Lück HJ, et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial[J]. Ann Oncol, 2018, 29(1):178-185.
[12] 梁江红, 冷小飞, 程萍, 等. 紫杉醇剂量密度方案化疗在上皮性卵巢癌应用的疗效及安全性meta分析[J].现代妇产科进展, 2015, 24(6): 416-420.
[13] 范淑英, 王健, 刘芸, 等. 紫杉醇联合卡铂周疗和三周疗法治疗卵巢癌的Meta分析[J]. 解放军医学杂志, 2016, 41(7): 589-597.
[14] Miller AB,Hongstraten B,Staquet M,et al. Reporting results of cancer treatment[J]. Cancer, 1981, 47(1): 207-214.
[15] National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Program. National Cancer Institute Common Toxicity Criteria, version 2.0. [EB/OL].https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm, /1999-4-30.
[16] Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8(1):16.
[17] Clamp AR, McNeish I, Dean A, et al. ICON8: a GCIG phase III randomised trial evaluating weekly dose-dense chemotherapy integration in firstline epithelial ovarian/fallopian tube/primary peritoneal carcinoma (EOC) treatment:results of primary progression free survival (PFS) analysis[C]. Ann Oncol (Meeting Abstracts), 2017, 28 (S5): v605–v649.
[18] Chan JK, Brady MF, Penson RT, et al. Weekly vs. every-3-Week paclitaxel and carboplatin for ovarian cancer[J]. N Engl J Med, 2016, 71(8):738-748.
[19] Du ZH, Ma XL. Dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin treatment for stage II-IV ovarian cancer patients[ J]. Bangladesh J Pharmacol, 2015, 10(3): 489-493.
[20] 贺凌云, 朱炜, 罗君玲, 等. 单周与3周紫杉醇联合卡铂方案治疗卵巢癌临床疗效分析[J]. 中国现代医药杂志, 2015,17(9):12-15.
[21] Pignata S,Scambia G,Katsaros D,et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet Oncol,2014, 15(4):396-405.
[22] Burg MEL, Onstenk W, Boere IA, et al. Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer[J]. Eur J Cancer, 2014, 50(15): 2592-2601.
[23] Katsumata N, Yasuda M, Isonishi S, et al. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial[J]. Lancet Oncol, 2013, 14(10):1020-1026.
[24] 陈为, 王善林, 周龙书, 等. 紫杉醇联合卡铂周疗和三周疗法治疗上皮性卵巢癌的疗效比较[J]. 中国现代医生, 2013, 51(17):37-39.
[25] 张冬梅, 闫玉兰, 王英, 等. 剂量密集化疗治疗晚期上皮性卵巢癌疗效观察[J]. 国际妇产科学杂志, 2013, 40(5):472-474.
[26] 刘云军, 何志江, 黄毅超, 等. 单周紫杉醇化疗方案在晚期卵巢癌的临床应用[J]. 中华全科医学, 2013, 11(8):1231-1232.
[27] 沈铿, 李孟达, 丰有吉, 等. 泰素周疗和三周疗法作为卵巢癌一线化疗的多中心对照研究[J]. 中华医学杂志, 2005, 85(30):2099-2103.
[28] Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review[J]. Cancer Biol Med, 2017, 14(1):9-32.
[29] National Comprehensive Cancer Network Guidelines Version 2.2018 Ovarian Cancer.[EB/OL].http://www.nccn.org.
[30] National Comprehensive Cancer Network Guidelines Version 3.2018 Breast Cancer. [EB/OL].http://www.nccn.org/patients.
[31] Loizzi V, Del Vecchio V, Crupano FM, et al. A phase II study: dose-dense carboplatin and paclitaxel as neoadjuvant chemotherapy in locally advanced cervical cancer[J]. J Chemother, 2018, 30(4): 247-252.
[32] Kogan L, Laskov I, Amajoud Z, et al. Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer[J]. Gynecol Oncol, 2017, 147(1): 30-35.
[33] Garcia CR, Slone SA, Morgan RM, et al. Dose-dense temozolomide for recurrent high-grade gliomas: a single-center retrospective study[J]. Med Oncol, 2018, 35(10):136-144.
[34] Zhu C, Liu J, Zhang J, et al. Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma[J]. Oncotarget, 2017, 8(41): 71117-71127.