舒尼替尼2/1方案与4/2方案治疗转移性肾癌临床研究Meta分析
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摘要
目的舒尼替尼4/2方案作为转移性肾癌(metastatic renal cell cancer,mRCC)的标准治疗方案,在治疗过程中会出现较多不良反应。为进一步说明舒尼替尼2/1方案的可行性,本研究通过Meta分析对舒尼替尼2/1方案与4/2方案治疗转移性肾癌疗效及不良反应进行系统评价。方法检索包括国内外已发表的病例对照研究。所检索的数据库包括Embase、PubMed、BioMed Central、Cinahl、中国知网、维普、万方和Cochrane Library等,检索期限为建库至2018-10-25。采用Review Manager 5.3进行数据分析。结果有6篇外文文献和1篇中文文献符合纳入标准,共417例患者。Meta分析结果显示,2/1方案与4/2方案在控制mRCC患者疾病稳定(OR=0.55,95%CI:0.34～0.89,P=0.01)、中性粒细胞减少(OR=2.70,95%CI:1.69～4.32,P<0.01)、白细胞减少(OR=1.97,95%CI:1.22～3.17,P<0.01)、贫血(OR=1.67,95%CI:1.12～2.50,P=0.01)、乏力(OR=3.85,95%CI:2.54～5.83,P<0.01)、高血压(OR=1.82,95%CI:1.25～2.65,P<0.01)、甲状腺功能低下(OR=1.90,95%CI:1.01～3.59,P=0.05)、手足综合征(OR=2.85,95%CI:1.61～5.04,P<0.01)和口腔炎或黏膜炎(OR=2.50,95%CI:1.36～4.59,P<0.01)方面比较,差异有统计学意义。2/1方案组3～4级血小板减少(OR=1.82,95%CI:1.03～3.23,P=0.04)、腹泻(OR=2.67,95%CI:1.01～7.10,P=0.05)和口腔炎或腹膜炎(OR=4.12,95%CI:1.25～13.52,P=0.02)发生率均低于4/2方案组,差异有统计学意义。结论舒尼替尼2/1方案与4/2方案比较,治疗mRCC疗效相当,但不良反应更少。上述结论尚需更多的大样本随机对照研究进一步加以验证。
OBJECTIVE As the standard treatment for metastatic renal cell cancer(mRCC),sunitinib schedule 4/2 will have more adverse reactions in the treatment process.In order to further illustrate the feasibility of schedule 2/1,this study systematically evaluated the efficacy and adverse reactions of sunitinib schedule 2/1 and schedule 4/2 in the treatment of mRCC through meta analysis.METHODS The databases retrieved included the published case control studies at home and abroad,including the Embase,PubMed,BioMed Central,Cinahl,Cochrane Library,etc.The retrieval time is from the database establishment to October 25,2018.the Review Manager 5.3 software was used for data analysis.RESULTS There were 6 foreign literatures,and 1 Chinese literatures met the inclusion criteria,a total of 417 patients.By meta analysis showed:compared with schedule 4/2,schedule 2/1 in controlling SD of mRCC patients(OR=0.55,95%CI:0.34-0.89,P=0.01),neutropenia(OR=2.70,95%CI:1.69-4.32,P<0.01),leukopenia(OR=1.97,95%CI:1.22-3.17,P<0.01),anemia(OR=1.67,95%CI:1.12-2.50,P=0.01),fatigue(OR=3.85,95%CI:2.54-5.83,P<0.01),hypertension(OR=1.82,95%CI:1.25-2.65,P<0.01),hypothyroidism(OR=1.90,95%CI:1.01-3.59,P=0.05),Hand-Foot syndrome(OR=2.85,95%CI:1.61-5.04,P<0.01),the stomatitis or mucosal inflammation(OR=2.50,95%CI:1.36-4.59.P<0.01)had statistically significant differences.The incidence of grade 3-4 thrombocytopenia(OR=1.82,95%CI:1.03-3.23,P=0.04),diarrhea(OR=2.67,95%CI:1.01-7.10,P=0.05),stomatitis or mucositis(OR=4.12,95%CI:1.25-13.52,P=0.02)in schedule 2/1 was lower than that in schedule 4/2,with statistically significant differences.CONCLUSION Schedule 2/1 and 4/2 have comparable efficacy in the treatment of mRCC,but can reduce the incidence of adverse reactions.
OBJECTIVE As the standard treatment for metastatic renal cell cancer(mRCC),sunitinib schedule 4/2 will have more adverse reactions in the treatment process.In order to further illustrate the feasibility of schedule 2/1,this study systematically evaluated the efficacy and adverse reactions of sunitinib schedule 2/1 and schedule 4/2 in the treatment of mRCC through meta analysis.METHODS The databases retrieved included the published case control studies at home and abroad,including the Embase,PubMed,BioMed Central,Cinahl,Cochrane Library,etc.The retrieval time is from the database establishment to October 25,2018.the Review Manager 5.3 software was used for data analysis.RESULTS There were 6 foreign literatures,and 1 Chinese literatures met the inclusion criteria,a total of 417 patients.By meta analysis showed:compared with schedule 4/2,schedule 2/1 in controlling SD of mRCC patients(OR=0.55,95%CI:0.34-0.89,P=0.01),neutropenia(OR=2.70,95%CI:1.69-4.32,P<0.01),leukopenia(OR=1.97,95%CI:1.22-3.17,P<0.01),anemia(OR=1.67,95%CI:1.12-2.50,P=0.01),fatigue(OR=3.85,95%CI:2.54-5.83,P<0.01),hypertension(OR=1.82,95%CI:1.25-2.65,P<0.01),hypothyroidism(OR=1.90,95%CI:1.01-3.59,P=0.05),Hand-Foot syndrome(OR=2.85,95%CI:1.61-5.04,P<0.01),the stomatitis or mucosal inflammation(OR=2.50,95%CI:1.36-4.59.P<0.01)had statistically significant differences.The incidence of grade 3-4 thrombocytopenia(OR=1.82,95%CI:1.03-3.23,P=0.04),diarrhea(OR=2.67,95%CI:1.01-7.10,P=0.05),stomatitis or mucositis(OR=4.12,95%CI:1.25-13.52,P=0.02)in schedule 2/1 was lower than that in schedule 4/2,with statistically significant differences.CONCLUSION Schedule 2/1 and 4/2 have comparable efficacy in the treatment of mRCC,but can reduce the incidence of adverse reactions.
引文
[1] Porta C,Gore ME,Rini BI,et al.Long-term safety of sunitinib in metastatic renal cell carcinoma[J].Eur Urol,2016,69(2):345-351.
[2] Inoue R,Kitamura H,Shindo T,et al.Dosing schedules and outcomes in patients treated with first-line sunitinib for advanced renal cell carcinoma[J].Hinyokika Kiyo,2016,62(4):173-177.
[3] Ezz El Din M.Sunitinib 4/2versus 2/1schedule for patients with metastatic renal cell carcinoma:tertiary care hospital experience[EB/OL].Clin Genitourin Cancer,2017,15(3):e455-e462[2018-01-04].https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1558767316303196?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS155876-7316303196%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F.
[4] Kondo T,Takagi T,Kobayashi H,et al.Superior tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-weekoff in patients with metastatic renal cell carcinoma--comparison to standard dosing schedule of 4-weeks-on and 2-weeks-off[J].Jpn J Clin Oncol,2014,44(3):270-277.
[5] Lee JL,Kim MK,Park I,et al.RandomizEd phaseⅡtrial of sunitinib four weeks on and two weeks off versus two weeks on and one week off in metastatic clear-cell type renal cell carcinoma:RESTORE trial[J].Ann Oncol,2015,26(11):2300-2305.
[6] Miyake H,Matsushita Y,Watanabe H,et al.Significance of introduction of alternative dosing schedule for sunitinib during first-line treatment of patients with metastatic renal cell carcinoma[J].Med Oncol,2018,35(10):133.
[7] Pan X,Huang H,Huang Y,et al.Sunitinib dosing schedule 2/1improves tolerability,efficacy,and health-related quality of life in Chinese patients with metastatic renal cell carcinoma[EB/OL].Urol Oncol,2015,33(6):268.e9-15[2017-04-08].https://www. clinicalkey. com/#!/content/playContent/1-s2. 0-S1078143915001167?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1078143915001167%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F.
[8] Zhang X,Sun G,Zhao J,et al.Improved long-term clinical outcomes and safety profile of sunitinib dosing schedule with 4/2switched to 2/1in patients with metastatic renal cell carcinoma[J].J Cancer,2018,9(18):3303-3310.
[9]潘秀武,干思舜,崔心刚,等.舒尼替尼2/1方案与4/2方案治疗转移性肾癌的疗效及对不良反应耐受性的对比分析[J].临床泌尿外科杂志,2015,30(3):218-221.
[10]施国海,姚旭东,张世林,等.舒尼替尼治疗转移性非透明细胞肾癌的疗效观察[J].中华泌尿外科杂志,2011,32(10):711-713.
[11] Prasad V,Massey PR,Fojo T.Oral anticancer drugs:how limited dosing options and dose reductions may affect outcomes in comparative trials and efficacy in patients[J].Clin Oncol,2014,32(15):1620-1629.
[12] Yoo C,Kim JE,Lee JL,et al.The efficacy and safety of sunitinib in korean patients with advanced renal cell carcinoma:high incidence of toxicity leads to frequent dose reduction[J].Jpn J Clin Oncol,2010,40(10):980-985.
[13] Najjar YG,Mittal K,Elson P,et,al.A 2weeks on and 1week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma[J].Eur J Cancer,2014,50(6):1084-1089.
[14] Tang SC,Lagas JS,Lankheet NA,et al.Brain accumulation of sunitinib is restricted by P-glycoprotein(ABCB1)and breast cancer resistance protein(ABCG2)and can be enhanced by oral elacridar and sunitinib coadministration[J].Int J Cancer,2012,130(1):223-233.
[15] Rini BI,Cohen DP,Lu DR,et al.Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib[J].J Natl Cancer Inst,2011,103(9):763-773.
[16] Guida FM,Santoni M,Conti A,et,al.Alternative dosing schedules for sunitinib as a treatment of patients with metastatic renal cell carcinoma[J].Crit Rev Oncol Hematol,2014,92(3):208-217.
[2] Inoue R,Kitamura H,Shindo T,et al.Dosing schedules and outcomes in patients treated with first-line sunitinib for advanced renal cell carcinoma[J].Hinyokika Kiyo,2016,62(4):173-177.
[3] Ezz El Din M.Sunitinib 4/2versus 2/1schedule for patients with metastatic renal cell carcinoma:tertiary care hospital experience[EB/OL].Clin Genitourin Cancer,2017,15(3):e455-e462[2018-01-04].https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1558767316303196?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS155876-7316303196%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F.
[4] Kondo T,Takagi T,Kobayashi H,et al.Superior tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-weekoff in patients with metastatic renal cell carcinoma--comparison to standard dosing schedule of 4-weeks-on and 2-weeks-off[J].Jpn J Clin Oncol,2014,44(3):270-277.
[5] Lee JL,Kim MK,Park I,et al.RandomizEd phaseⅡtrial of sunitinib four weeks on and two weeks off versus two weeks on and one week off in metastatic clear-cell type renal cell carcinoma:RESTORE trial[J].Ann Oncol,2015,26(11):2300-2305.
[6] Miyake H,Matsushita Y,Watanabe H,et al.Significance of introduction of alternative dosing schedule for sunitinib during first-line treatment of patients with metastatic renal cell carcinoma[J].Med Oncol,2018,35(10):133.
[7] Pan X,Huang H,Huang Y,et al.Sunitinib dosing schedule 2/1improves tolerability,efficacy,and health-related quality of life in Chinese patients with metastatic renal cell carcinoma[EB/OL].Urol Oncol,2015,33(6):268.e9-15[2017-04-08].https://www. clinicalkey. com/#!/content/playContent/1-s2. 0-S1078143915001167?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1078143915001167%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F.
[8] Zhang X,Sun G,Zhao J,et al.Improved long-term clinical outcomes and safety profile of sunitinib dosing schedule with 4/2switched to 2/1in patients with metastatic renal cell carcinoma[J].J Cancer,2018,9(18):3303-3310.
[9]潘秀武,干思舜,崔心刚,等.舒尼替尼2/1方案与4/2方案治疗转移性肾癌的疗效及对不良反应耐受性的对比分析[J].临床泌尿外科杂志,2015,30(3):218-221.
[10]施国海,姚旭东,张世林,等.舒尼替尼治疗转移性非透明细胞肾癌的疗效观察[J].中华泌尿外科杂志,2011,32(10):711-713.
[11] Prasad V,Massey PR,Fojo T.Oral anticancer drugs:how limited dosing options and dose reductions may affect outcomes in comparative trials and efficacy in patients[J].Clin Oncol,2014,32(15):1620-1629.
[12] Yoo C,Kim JE,Lee JL,et al.The efficacy and safety of sunitinib in korean patients with advanced renal cell carcinoma:high incidence of toxicity leads to frequent dose reduction[J].Jpn J Clin Oncol,2010,40(10):980-985.
[13] Najjar YG,Mittal K,Elson P,et,al.A 2weeks on and 1week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma[J].Eur J Cancer,2014,50(6):1084-1089.
[14] Tang SC,Lagas JS,Lankheet NA,et al.Brain accumulation of sunitinib is restricted by P-glycoprotein(ABCB1)and breast cancer resistance protein(ABCG2)and can be enhanced by oral elacridar and sunitinib coadministration[J].Int J Cancer,2012,130(1):223-233.
[15] Rini BI,Cohen DP,Lu DR,et al.Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib[J].J Natl Cancer Inst,2011,103(9):763-773.
[16] Guida FM,Santoni M,Conti A,et,al.Alternative dosing schedules for sunitinib as a treatment of patients with metastatic renal cell carcinoma[J].Crit Rev Oncol Hematol,2014,92(3):208-217.