复方环磷酰胺片节拍疗法联合沙利度胺治疗高龄进展期卵巢癌7例临床分析
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摘要
目的探讨复方环磷酰胺片节拍疗法联合沙利度胺治疗高龄进展期卵巢癌患者的临床疗效与安全性。方法 7例高龄进展期卵巢癌患者,采用口服复方环磷酰胺片50 mg/d,沙利度胺片以100 mg/d为起始剂量,每晚睡前服用,视病人耐受毒副反应情况,逐渐增至150 mg/d维持治疗,如不能耐受加量则维持原剂量。每4周为一周期,每2周期评估疗效,同时观察毒副反应。结果 (1)7例患者均接受6个周期以上的治疗,5例获PR,2例获SD,ORR为71.4%(5/7),DCR为100%(7/7),中位OS为40月(18~56月)。(2)主要不良反应为Ⅰ~Ⅱ度血液学毒性、便秘与末梢神经炎,以及Ⅰ度出血性膀胱炎,经对症处理好转,未调整药物剂量。结论复方环磷酰胺片节拍疗法联合沙利度胺治疗高龄进展期卵巢癌,临床疗效较好且无明显毒副作用,具有潜在的应用前景。
Objective To explore the efficacy and safety of the regimen of metronomic chemotherapy with cyclophosphamide plus thalidomide in elderly patients with advanced ovarian cancer. Methods Seven consecutive elderly patients with advanced ovarian cancer were treated with the regimen of metronomic chemotherapy with cyclophosphamide(50 mg/d) plus thalidomide(100~150 mg/d).The efficacy was assessed every two cycles and every four weeks was termed as one cycle. Also, the adverse effects were recorded. Results(1)All the patients received treatment with over 6 cycles. Five cases achieved partial remission and two achieved stable disease. The overall response rate(ORR) was 71.4% and the disease control rate(DCR) was 100%.The median overall survival(OS) was 40 months(ranging from 18~56 months).(2)The main adverse effects were grade 1~2 hematological toxicities,constipation and peripheral neuritis,as well as grade1 hemorrhagic cystitis. The toxicities were alleviated after symptomatic treatment without decrease of drug dose. Conclusion The regimen of metronomic chemotherapy with cyclophosphamide plus thalidomide cause high efficacy without significant toxicities,which merits further studies.
Objective To explore the efficacy and safety of the regimen of metronomic chemotherapy with cyclophosphamide plus thalidomide in elderly patients with advanced ovarian cancer. Methods Seven consecutive elderly patients with advanced ovarian cancer were treated with the regimen of metronomic chemotherapy with cyclophosphamide(50 mg/d) plus thalidomide(100~150 mg/d).The efficacy was assessed every two cycles and every four weeks was termed as one cycle. Also, the adverse effects were recorded. Results(1)All the patients received treatment with over 6 cycles. Five cases achieved partial remission and two achieved stable disease. The overall response rate(ORR) was 71.4% and the disease control rate(DCR) was 100%.The median overall survival(OS) was 40 months(ranging from 18~56 months).(2)The main adverse effects were grade 1~2 hematological toxicities,constipation and peripheral neuritis,as well as grade1 hemorrhagic cystitis. The toxicities were alleviated after symptomatic treatment without decrease of drug dose. Conclusion The regimen of metronomic chemotherapy with cyclophosphamide plus thalidomide cause high efficacy without significant toxicities,which merits further studies.
引文
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[14]Cascales-Campos P,Gil J,Gil E,et al.Cytoreduction and HIPEC after neoadjuvant chemotherapy in stage IIIC-IV ovarian cancer.Critical analysis in elderly patients[J].Eur J Obstet Gynecol Reprod Biol,2014,179:88-93.
[15]Delotte J,Arias T,Guerin O,etal.Hyperthermic intraperitoneal chemotherapy for the treatment of recurrent ovarian cancer in elderly women[J].Acta Obstet Gynecol Scand,2015,94(4):435-439.
[16]Scharovsky O G,Mainetti L E,Rozados V R.Metronomic chemotherapy:changing the paradigm that more is better[J].Curr Oncol,2009,16(2):7-15.
[17]Perroud H A,Rico M J,Alasino C M,et al.Association between baseline VEGF/s VEGFR-2 and VEGF/TSP-1ratios and response to metronomic chemotherapy using cyclophosphamide and celecoxib in patients with advanced breast cancer[J].Indian J Cancer,2013,50(2):115-121.
[18]Yabu T,Tomimoto H,Taguchi Y,et al.Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors,and is antagonized by sphingosine-1-phosphate[J].Blood,2005,106(1):125-134.
[19]Mpekris F,Baish J W,Stylianopoulos T,et al.Role of vascular normalization in benefit from metronomic chemotherapy[J].Proc Natl Acad Sci USA,2017,114(8):1994-1999.
[20]Wang X,Shen Y,Li S,et al.Importance of the interaction between immune cells and tumor vasculature mediated by thalidomide in cancer treatment(Review)[J].Int J Mol Med,2016,38(4):1021-1029.
[2]Giri S K,Nayak B.Management of Ovarian Cancer in Elderly[J].Rev Recent Clin Trials,2015,10(4):270-275.
[3]Andre N,Tsai K,Carre M,etal.Metronomic Chemotherapy:Direct Targeting of Cancer Cells after all?[J].Trends Cancer,2017,3(5):319-325.
[4]Bocci G,Kerbel R S.Pharmacokinetics of metronomic chemotherapy:a neglected but crucial aspect[J].Nat Rev Clin Oncol,2016,13(11):659-673.
[5]Javadi S,Ganeshan D M,Qayyum A,et al.Ovarian Cancer,the Revised FIGO Staging System,and the Role of Imaging[J].AJR Am J Roentgenol,2016,206(6):1351-1360.
[6]Alexander V M,Gordon A N,Howard D H,et al.Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for Women With Recurrent Ovarian Cancer[J].Int J Gynecol Cancer,2017.
[7]Samaritani R,Corrado G,Vizza E,et al.Cyclophosphamide"metronomic"chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer[J].BMC Cancer,2007,7:65.
[8]Ferrandina G,Corrado G,Mascilini F,et al.Metronomic oral cyclophosphamide(MOC)in the salvage therapy of heavily treated recurrent ovarian cancer patients:a retrospective,multicenter study[J].BMC Cancer,2014,14:947.
[9]Shen W,Li H L,Liu L,etal.Expression levels of PTEN,HIF-1alpha,and VEGF as prognostic factors inovarian cancer[J].EurRev Med Pharmacol Sci,2017,21(11):2596-2603.
[10]Barber E L,Zsiros E,Lurain J R,et al.The combination of intravenousbevacizuma band metronomicoral cyclophosphamide is an effective regimen for platinumr esistantre current ovarian cancer[J].JGynecol Oncol,2013,24(3):258-264.
[11]Kareva I,Waxman DJ,Lakka K G.Metronomic chemotherapy:an attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance[J].Cancer Lett,2015,358(2):100-106.
[12]Gordinier M E,Dizon D S,Weitzen S,et al.Oral thalidomide as palliative chemotherapy in women with advanced ovarian cancer[J].J Palliat Med,2007,10(1):61-66.
[13]张莉莉,陈萍,谢勋鹏,等.沙利度胺改善晚期恶性肿瘤恶液质的临床观察[J].中国执业药师,2016(12):3-6.
[14]Cascales-Campos P,Gil J,Gil E,et al.Cytoreduction and HIPEC after neoadjuvant chemotherapy in stage IIIC-IV ovarian cancer.Critical analysis in elderly patients[J].Eur J Obstet Gynecol Reprod Biol,2014,179:88-93.
[15]Delotte J,Arias T,Guerin O,etal.Hyperthermic intraperitoneal chemotherapy for the treatment of recurrent ovarian cancer in elderly women[J].Acta Obstet Gynecol Scand,2015,94(4):435-439.
[16]Scharovsky O G,Mainetti L E,Rozados V R.Metronomic chemotherapy:changing the paradigm that more is better[J].Curr Oncol,2009,16(2):7-15.
[17]Perroud H A,Rico M J,Alasino C M,et al.Association between baseline VEGF/s VEGFR-2 and VEGF/TSP-1ratios and response to metronomic chemotherapy using cyclophosphamide and celecoxib in patients with advanced breast cancer[J].Indian J Cancer,2013,50(2):115-121.
[18]Yabu T,Tomimoto H,Taguchi Y,et al.Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors,and is antagonized by sphingosine-1-phosphate[J].Blood,2005,106(1):125-134.
[19]Mpekris F,Baish J W,Stylianopoulos T,et al.Role of vascular normalization in benefit from metronomic chemotherapy[J].Proc Natl Acad Sci USA,2017,114(8):1994-1999.
[20]Wang X,Shen Y,Li S,et al.Importance of the interaction between immune cells and tumor vasculature mediated by thalidomide in cancer treatment(Review)[J].Int J Mol Med,2016,38(4):1021-1029.