二线阿西替尼治疗晚期肾癌患者的疗效及不良反应
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摘要
目的:评价二线阿西替尼治疗晚期肾癌患者的疗效及安全性。方法:回顾性分析2009年10月～2011年9月于我院泌尿外科诊治的15例接受二线阿西替尼治疗的晚期肾癌患者。所有患者均接受肾根治性切除手术,病理均为透明细胞癌。11例患者一线舒尼替尼治疗后进展,4例患者一线免疫治疗后进展。二线治疗方案:初始剂量5mg、2次/d,连续4周为一周期直至疾病再次进展或不可耐受的严重毒副反应。若患者对药物耐受好,剂量可增至7mg、2次/d,或10mg、2次/d,若毒副反应重则剂量减至3mg、2次/d。结果:Kaplan-Meier生存分析提示这15例患者中位总位生存期(OS)23.0(18.0～28.0)个月。二线阿西替尼治疗的中位无进展生存期(PFS)为7.0(1.5～47.0)个月。根据RECIST标准评价最佳疗效:完全缓解(CR)0例(0),部分缓解(PR)3例(20.0%),疾病稳定(SD)8例(53.3%),疾病进展(PD)4例(26.7%)。多数不良反应多为1～2级,3～4级不良反应有蛋白尿2例(13.3%),腹泻1例(6.7%),呕吐2例(13.3%),乏力消瘦2例(13.3%),高血压5例(33.3%),手足皮肤反应1例(6.7%),口腔黏膜炎1例(6.7%),肝酶升高1例(6.7%),脑梗死1例(6.7%),上消化道出血1例(6.7%)。通过减量或暂停药,多数不良反应可以耐受。结论:二线阿西替尼治疗晚期肾癌可取得较长的OS和PFS,二线治疗有较高疾病控制率,且不良反应多可耐受。
Objective:To investigate the efficacy and safety of axitinib in the treatment of advanced renal cell carcinoma.Method:A retrospective study of 15 patients with advanved renal cell carcinoma treated with secondline axitinib in Peking University First Hospital between Oct.2009 and Sep.2011.All patients underwent radical nephrectomy and the pathological characteristics are all clear cell carcinomas.Eleven cases received sunitinib as first-line therapy,and another 4 cases received first-line immunotherapy.But they all experienced disease progression.Second-line axitinib was administered 5 mg twice daily,four weeks a period repeatedly until disease progression or severe adverse effect occurred.For patients without severe adverse effect 7 mg twice daily or even10 mg twice daily monotherapy can be used.Dose reduction to 3 mg twice daily can also be used if needed.Result:The median overall survival of the 15 patients was 23.0(range,18.0-28.0)months,and the median progression free surival was 7.0(range,1.5-47.0)months.The best efficacy results showed:0 patient(0)achieved complete recession,3 patients(20.0%)experienced partial recession,8 patients(53.3%)showed stable disease,4 patients(26.7%)developed progressive disease.Most adverse effects were graded 1 or 2.Severe adverse effects included 2(13.3%)patients with proteinuria,1(6.7%)patient with diarrhea,2(13.3%)patients with vomiting,2(13.3%)patients with weight decreased and fatigue,5(33.3%)patients with hypertension,1(6.7%)patient with hand-foot syndrome,1(6.7%)patient with mucosal inflammation,1(6.7%)patient with decreased liver function,1(6.7%)patient with cerebral thrombosis,1(6.7%)patient with upper gastrointestinal bleeding.Most adverse effects were ameliorated by dose reduction or temporary drug interruption.Conclusion:The study shows second-line axitinib can achieve promising OS and PFS for Chinese patients with advanced renal cell carcinoma,with satisfactory efficacy and manageable adverse effect events.
Objective:To investigate the efficacy and safety of axitinib in the treatment of advanced renal cell carcinoma.Method:A retrospective study of 15 patients with advanved renal cell carcinoma treated with secondline axitinib in Peking University First Hospital between Oct.2009 and Sep.2011.All patients underwent radical nephrectomy and the pathological characteristics are all clear cell carcinomas.Eleven cases received sunitinib as first-line therapy,and another 4 cases received first-line immunotherapy.But they all experienced disease progression.Second-line axitinib was administered 5 mg twice daily,four weeks a period repeatedly until disease progression or severe adverse effect occurred.For patients without severe adverse effect 7 mg twice daily or even10 mg twice daily monotherapy can be used.Dose reduction to 3 mg twice daily can also be used if needed.Result:The median overall survival of the 15 patients was 23.0(range,18.0-28.0)months,and the median progression free surival was 7.0(range,1.5-47.0)months.The best efficacy results showed:0 patient(0)achieved complete recession,3 patients(20.0%)experienced partial recession,8 patients(53.3%)showed stable disease,4 patients(26.7%)developed progressive disease.Most adverse effects were graded 1 or 2.Severe adverse effects included 2(13.3%)patients with proteinuria,1(6.7%)patient with diarrhea,2(13.3%)patients with vomiting,2(13.3%)patients with weight decreased and fatigue,5(33.3%)patients with hypertension,1(6.7%)patient with hand-foot syndrome,1(6.7%)patient with mucosal inflammation,1(6.7%)patient with decreased liver function,1(6.7%)patient with cerebral thrombosis,1(6.7%)patient with upper gastrointestinal bleeding.Most adverse effects were ameliorated by dose reduction or temporary drug interruption.Conclusion:The study shows second-line axitinib can achieve promising OS and PFS for Chinese patients with advanced renal cell carcinoma,with satisfactory efficacy and manageable adverse effect events.
引文
1 Rini B I,Campbell S C,Escudier B.Renal cell carcinoma[J].Lancet,2009,373(9669):1119-1132.
2 Ljungberg B,Bensalah K,Canfield S,et al.EAU guidelines on renal cell carcinoma:2014update[J].Eur Urol,2015,67(5):913-924.
3 Powles T,Albiges L,Staehler M,et al.Updated European Association of Urology Guidelines Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer[J].Eur Urol,2017.
4 He Z,Guo G,Zhang C,et al.Efficacy of sunitinib in patients with metastatic renal cell carcinoma:initial experience in two Chinese centers[J].Chin Med J(Engl),2014,127(8):1450-1453.
5 Powles T,Staehler M,Ljungberg B,et al.Updated EAUGuidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy[J].Eur Urol,2016,69(1):4-6.
6 Therasse P,Arbuck S G,Eisenhauer E A,et al.New guidelines to evaluate the response to treatment in solid tumors.European Organization for Research and Treatment of Cancer,National Cancer Institute of the United States,National Cancer Institute of Canada[J].J Natl Cancer Inst,2000,92(3):205-216.
7 Cohen H T,McGovern F J.Renal-cell carcinoma[J].NEngl J Med,2005,353(23):2477-2490.
8 Yu X,Guo G,Li X,et al.Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival[J].Medicine(Baltimore),2015,94(34):e1361-e1361.
9 Li X S,Wu X,Zhao P J,et al.Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma[J].Chin Med J(Engl),2011,124(18):2920-2924.
10董毅,琚官群.转移性肾非透明细胞癌靶向治疗进展[J].临床泌尿外科杂志,2018,33(10):841-845.
11 Rini B I,Escudier B,Tomczak P,et al.Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma(AXIS):a randomised phase 3trial[J].Lancet,2011,378(9807):1931-1939.
12 Motzer R J,Escudier B,Tomczak P,et al.Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma:overall survival analysis and updated results from a randomised phase 3trial[J].Lancet Oncol,2013,14(6):552-562.
13 Ueda T,Uemura H,Tomita Y,et al.Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma:subgroup analysis of Japanese patients from the global randomized Phase 3AXIS trial[J].Jpn J Clin Oncol,2013,43(6):616-628.
14 Fujiwara Y,Kiyota N,Chayahara N,et al.Management of axitinib(AG-013736)-induced fatigue and thyroid dysfunction,and predictive biomarkers of axitinib exposure:results from phase I studies in Japanese patients[J].Invest New Drugs,2012,30(3):1055-1064.
15张金超,王丹红.转移性肾癌的临床治疗进展[J].临床泌尿外科杂志,2016,31(6):574-579.
16 Choueiri T K,Escudier B,Powles T,et al.Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma[J].N Engl J Med,2015,373(19):1814-1823.
17 Choueiri T K,Escudier B,Powles T,et al.Cabozantinib versus everolimus in advanced renal cell carcinoma(METEOR):final results from a randomised,open-label,phase 3trial[J].Lancet Oncol,2016,17(7):917-927.
18 Choueiri T K,Larkin J,Oya M,et al.Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma(JAVELIN Renal 100):an open-label,dose-finding and dose-expansion,phase 1btrial[J].Lancet Oncol,2018,19(4):451-460.
2 Ljungberg B,Bensalah K,Canfield S,et al.EAU guidelines on renal cell carcinoma:2014update[J].Eur Urol,2015,67(5):913-924.
3 Powles T,Albiges L,Staehler M,et al.Updated European Association of Urology Guidelines Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer[J].Eur Urol,2017.
4 He Z,Guo G,Zhang C,et al.Efficacy of sunitinib in patients with metastatic renal cell carcinoma:initial experience in two Chinese centers[J].Chin Med J(Engl),2014,127(8):1450-1453.
5 Powles T,Staehler M,Ljungberg B,et al.Updated EAUGuidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy[J].Eur Urol,2016,69(1):4-6.
6 Therasse P,Arbuck S G,Eisenhauer E A,et al.New guidelines to evaluate the response to treatment in solid tumors.European Organization for Research and Treatment of Cancer,National Cancer Institute of the United States,National Cancer Institute of Canada[J].J Natl Cancer Inst,2000,92(3):205-216.
7 Cohen H T,McGovern F J.Renal-cell carcinoma[J].NEngl J Med,2005,353(23):2477-2490.
8 Yu X,Guo G,Li X,et al.Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival[J].Medicine(Baltimore),2015,94(34):e1361-e1361.
9 Li X S,Wu X,Zhao P J,et al.Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma[J].Chin Med J(Engl),2011,124(18):2920-2924.
10董毅,琚官群.转移性肾非透明细胞癌靶向治疗进展[J].临床泌尿外科杂志,2018,33(10):841-845.
11 Rini B I,Escudier B,Tomczak P,et al.Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma(AXIS):a randomised phase 3trial[J].Lancet,2011,378(9807):1931-1939.
12 Motzer R J,Escudier B,Tomczak P,et al.Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma:overall survival analysis and updated results from a randomised phase 3trial[J].Lancet Oncol,2013,14(6):552-562.
13 Ueda T,Uemura H,Tomita Y,et al.Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma:subgroup analysis of Japanese patients from the global randomized Phase 3AXIS trial[J].Jpn J Clin Oncol,2013,43(6):616-628.
14 Fujiwara Y,Kiyota N,Chayahara N,et al.Management of axitinib(AG-013736)-induced fatigue and thyroid dysfunction,and predictive biomarkers of axitinib exposure:results from phase I studies in Japanese patients[J].Invest New Drugs,2012,30(3):1055-1064.
15张金超,王丹红.转移性肾癌的临床治疗进展[J].临床泌尿外科杂志,2016,31(6):574-579.
16 Choueiri T K,Escudier B,Powles T,et al.Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma[J].N Engl J Med,2015,373(19):1814-1823.
17 Choueiri T K,Escudier B,Powles T,et al.Cabozantinib versus everolimus in advanced renal cell carcinoma(METEOR):final results from a randomised,open-label,phase 3trial[J].Lancet Oncol,2016,17(7):917-927.
18 Choueiri T K,Larkin J,Oya M,et al.Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma(JAVELIN Renal 100):an open-label,dose-finding and dose-expansion,phase 1btrial[J].Lancet Oncol,2018,19(4):451-460.