术中应用5-Fu缓释剂治疗晚期卵巢癌的近期疗效观察
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摘要
【目的】:探讨术中运用缓释氟尿嘧啶治疗晚期卵巢癌的近期疗效和毒副反应。【方法】:对南京鼓楼医院2006年9月—2009年10月期间收治的62例晚期卵巢癌患者进行回顾分析,分为两组,术中植入5-Fu缓释剂+TP化疗组30例和TP化疗组32例。【结果】:两组术前的CA_125水平比较,差异均无统计学意义(P>0.05)。5- Fu缓释剂+TP组平均CA_125值降至22.5 U/ml,TP化疗组CA_125值降至57.7 U/ml(P<0.05),但第2次、第3次或第4次化疗后两组的CA_125水平比较,差异无统计学意义(P>0.05)。初治卵巢癌患者的5-Fu缓释剂+TP组与TP组,第1次化疗后,5- Fu缓释剂+TP组平均CA_125值降至15.6 U/ml,TP化疗组CA_125值降至33.7 U/ml(P<0.05),复发卵巢癌患者经第1次或第2次化疗后,5- Fu缓释剂+TP组平均CA_125值分别降至24.5U/ml、21.4 U/ml,TP化疗组CA_125值分别降至66.5U/ml、44.4 U/ml(P<0.05)。5-Fu缓释剂+TP组治疗后腹水有效率为68%,盆腔肿块有效率47%,淋巴结转移者有效率30%。两组在白细胞减少、贫血,血小板减少、胃肠道反应,肝功能损害、肾功能损害及脱发等方面比较,差异均无统计学意义(P>0.05)。5- Fu缓释剂+TP组中6例(20%)术后出现刺激性腹痛,但患者可以耐受。【结论】:在经过理想的肿瘤细胞减灭术的晚期卵巢癌患者中,术中运用5-Fu缓释剂腹腔化疗有效可行,特别是对复发性卵巢癌有较好的近期疗效,且不增加患者的毒副反应.临床上可以接受。
【Objective】To evaluate the efficacy and side effects of sustained-release 5-Fluorouracil used during operation in the treatment of advanced ovarian elithelial carcinoma.【Methods】Retrospective analysis was utilized to analyze the clinical materials of 62 cases of advanced ovarian cancer in the Nanjing Drum Tower hospital from September 2006 to October 2009,Divided into two groups,30 cases in the group of sustained-release 5-Fluorouracil used during operation combined with TP chemotherapy after operation,and 32 cases in the group of TP chemotherapy after operation.【Result】Preoperative CA_125 levels of the two groups, the difference was not statistically significan(tP>0.05).After the first cycle chemotherapy,CA_125 levels in sustained-release 5-Fluorouracil combined with TP chemotherapy group were lower than that in TP chemotherapy group(P<0.05),but there were no significant difference between two groups after second,third or fourth cycle chemotherapy(P> 0.05).For First treatment ovarian cancer patients,CA_125 levels in sustained-release 5-Fluorouracil combined with chemotherapy group were lower than that in TP chemotherapy group after first cycle(P<0.05),for the patients with recurrent ovarian cancer,CA_125 levels in sustained-release 5-Fluorouracil combined with TP chemotherapy group were lower than that in TP chemotherapy group after first cycle(P<0.05).After sustained-release 5-Fluorouracil combined with TP chemotherapy treatment, Ascites effective rate was 68%, Pelvic mass was 47% efficiency, Lymph node metastasis rate was 30%,but there were no significant differences between two groups in the toxicities of hypoleukemia, anemia, thrombocytopenia digestive disturbance,liver function damage,renal function damage,phalacrosis (P>0.05)But 6 cases had postoperative abdominal pain stimulation in sustained-release 5-Fluorouracil combined with TP chemotherapy group,but can be tolerated.
【Conclusion】Intraoperative use of sustained-release 5-Fluorouracil intraperitoneal chemotherapy was effective and feasible for the advanced ovarian cancer after optimally cytoreductive surgery,In particular to recurrent ovarian cancer,and does not increase toxicity in patients ,so it can be clinically acceptable.
【Objective】To evaluate the efficacy and side effects of sustained-release 5-Fluorouracil used during operation in the treatment of advanced ovarian elithelial carcinoma.【Methods】Retrospective analysis was utilized to analyze the clinical materials of 62 cases of advanced ovarian cancer in the Nanjing Drum Tower hospital from September 2006 to October 2009,Divided into two groups,30 cases in the group of sustained-release 5-Fluorouracil used during operation combined with TP chemotherapy after operation,and 32 cases in the group of TP chemotherapy after operation.【Result】Preoperative CA_125 levels of the two groups, the difference was not statistically significan(tP>0.05).After the first cycle chemotherapy,CA_125 levels in sustained-release 5-Fluorouracil combined with TP chemotherapy group were lower than that in TP chemotherapy group(P<0.05),but there were no significant difference between two groups after second,third or fourth cycle chemotherapy(P> 0.05).For First treatment ovarian cancer patients,CA_125 levels in sustained-release 5-Fluorouracil combined with chemotherapy group were lower than that in TP chemotherapy group after first cycle(P<0.05),for the patients with recurrent ovarian cancer,CA_125 levels in sustained-release 5-Fluorouracil combined with TP chemotherapy group were lower than that in TP chemotherapy group after first cycle(P<0.05).After sustained-release 5-Fluorouracil combined with TP chemotherapy treatment, Ascites effective rate was 68%, Pelvic mass was 47% efficiency, Lymph node metastasis rate was 30%,but there were no significant differences between two groups in the toxicities of hypoleukemia, anemia, thrombocytopenia digestive disturbance,liver function damage,renal function damage,phalacrosis (P>0.05)But 6 cases had postoperative abdominal pain stimulation in sustained-release 5-Fluorouracil combined with TP chemotherapy group,but can be tolerated.
【Conclusion】Intraoperative use of sustained-release 5-Fluorouracil intraperitoneal chemotherapy was effective and feasible for the advanced ovarian cancer after optimally cytoreductive surgery,In particular to recurrent ovarian cancer,and does not increase toxicity in patients ,so it can be clinically acceptable.
引文
[1] Jemal A,Siegel R,Ward E,et al.Cancer statistics,2007.CA Cancer J Clin,2007,57(1):43-66.
[2] Faul C,Gersten K,Edwards R,et a1.A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome.Int J Radiat Oncol Biol Phys ,2000,7:749-754.
[3]曹泽毅.中华妇产科学.第二版北京:人民卫生出版社,2OO5:1640-1641.
[4]糜若然.现代妇科肿瘤诊疗手册.天津科学技术出版社,2001,115-150.
[5]乐杰.妇产科学.第七版.北京.人民卫生出版社.2008:282-284.
[6]沈铿.复发性卵巢癌的诊断和治疗策略.现代妇产科进展.2005,5(14).177-180.
[7] F.Gieseler P,Rudolph G .KloeppelU,et al .Resistance mechanisms of ovarian cancers : why does conventional chemotheraphy fail ? Int J Colorectal Dis.2003,18:470-480.
[8]李同度.临床肿瘤学.安徽科学出版社.1992:48-50.
[9] Nurten Gunduz ,Beruard Fisher,Elizabeth A.Saffer. Effect of surgical Removal on the growth and Kinetics of Residual Tumor.CANCER research,1979,39:3861-3865.
[10]孙燕,汤钊猷等.UICC《临床肿瘤学手册》.第8版.人民卫生出版社,2006:455-457.
[11] Motoya T.Biological characterization including sensitivity to mitomycin C of culured human ovarian cancers.Nippon Sanka Fujinka Gakkai Zasshi.1981,33(8):119 7-2004.
[12] Matkman M,Reichman B,Hares T,et al..Intraperitoneal Chemotherapy in the Management of Ovarian Cancer.Cancer,1993,71(4):1565~1570.
[13]沈铿,郎景和,等.卵巢癌化疗的现状和展望.中华妇产科杂志.1994,29(12):755～756.
[14]连利娟.卵巢癌化疗的现状与趋向.中华妇产科杂志.1996,31(2):67～70.
[15]杨纪华.循环热灌注化疗治疗恶性腹腔积液疗效观察.西安.第四军医大学.2009.
[16]刘会波,王仁友等.间质化疗临床应用研究进展.中国肿瘤.2005,3(14):174-177.
[17]朱雯怡,范跃祖,阎波,等.结肠旁植入氟尿嘧啶缓释剂化疗的药代动力学实验研究.中国肿瘤, 2007; 16: 63-65.
[18]洪艳艳,陈振东,等.氟尿嘧啶植入剂治疗恶性胸腹水的药代动力学研究.中国临床药理学杂志.2009,7:298-301.
[19]王波.关于5-Fu应用者血压计药浓度监测的研究..实用肿瘤杂志.1993,8(3):185-187.
[20]李井泉,赵平,等.5-氟尿嘧啶缓释化疗药代动力学研究.中国全科医学. 2007.10:630-631.
[21]Tuxen MK,Soletormos G Dombernowsky P.Tumor markers in the management of patients with ovarian cancer.Cancer Treat Rev,1995.21(3):215-245.
[22] Colombo N ,Parma G,Boeeiolone L,et.a1.Medical therapy of advanced malignant epithelial tumors of the ovary.Forum(Genova),2000,10:323—332.
[1] Jemal A,Siegel R,Ward E,et a1.Cancer statistics,2006.[J].CA Cancer J Clin.2006,56(2):106—130.
[2] Bristow RE,Tomaoruz RS,Armstrong DK,et a1.Survival effect of maximal eytoreduetive surgery for advanced ovadan carcinoma during the platinum era:a meta—analysis.[J].J Clin Oncol.2002,20(5):1248—1259.
[3]颜萍,何畏.化疗对卵巢癌患者免疫功能的影响.重庆医学.2002,31(7):597—604.
[4] WeinbergBD,Ai H,Blanco E,et al.Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods[J]. Bioed Mater Res A,2007,81(1):161-70.
[5] Rapoport N.Combined cancer therapy by micellar - encapsulated drug and ultrasound.[J].Int J Pharm,2004,277(122):155-62.
[6] Rapoport N,Gao Z,KennedyA.Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy[J].J Natl Cancer Inst.2007,99(14):1095 -1106.
[7] Nasongkla N, Wiedmann AF, Bruening A,et al.Enhancement of solubility and bioavailability of beta-lapachone using cyclodextrin inclusion complexes[J].Pharm Res,2003,20(10):1626-1633.
[8] Kan P,Lin XZ,Hsieh MF,et al.Thermogelling emulsions for vascular embolization and sustained release of drugs.[J].Biomed Mater Res B Appl Biomater.2005,75(1):185-92.
[9] Blanco E,Qian F,Weinberg B,et al.Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers.[J].Biomed Mater Res A,2004,69(3):398-406.
[10] Sinha VR ,et al.Chitosan microspheres as a potential carrier for drugs.[J].Int J Pharm.2004,274(1-2)∶136-140.
[11] Ruel-Gariepy E,et al.A thermosensitive chitosan–based hydrogel for the local delivery of paclitaxel.[J].Eur J Pharm Biop-harm,2004, 57(1)∶153-162.
[12] Qian F,Stowe N,Liu EH,et al.Quantification of in vivo doxorubicin transport from PLGA millirods in thermoablated rat livers.[J].Control Release,2003,91(122):157-166.
[13] AhmedM,Liu Z,LukyanovAN,etal.Combination radiofrequency ablation with intratumoral liposomal doxorubicin:effect on drug accumulation and coagulation in multiple tissues and tumor types in animals.[J]. Radiology.2005,235(2):469-477.
[14] Vassileva V, Allen CJ,et al.Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer.[J].Mol Cancer Ther.2008;7(3):630-637.
[15] Vassileva V,Moriyama EH,et al.Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.[J].Br J Cancer.2008,99(12): 2037-2043.
[16] Lu Z,Tsai M,et al.Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer.[J].J Pharmacol Exp Ther. 2008,327(3):673-682.
[17]Vassileva V,Grant J,et al.Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model.[J].Cancer Chemother Pharmacol.2007,60(6):907-914.
[18]Lu H,Li B,et al.Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting.[J]. Cancer Chemother Pharmacol.2007 ,59(2):175-181.
[19]陈峥峥,凌斌等.5-Fu缓释剂局部埋植治疗卵巢癌腹膜后转移的实验研究.[J].安徽医科大学学报.2005,40(6):538-540.
[20]Armstrong DK,Fleming GF,et al.A phase I trial of intraperitoneal sustained-release paclitaxel microspheres(Paclimer) in recurrent ovarian cancer: aGynecologic Oncology Group study.[J].Gynecol Oncol. 2006,103(2):391-396.
[2] Faul C,Gersten K,Edwards R,et a1.A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome.Int J Radiat Oncol Biol Phys ,2000,7:749-754.
[3]曹泽毅.中华妇产科学.第二版北京:人民卫生出版社,2OO5:1640-1641.
[4]糜若然.现代妇科肿瘤诊疗手册.天津科学技术出版社,2001,115-150.
[5]乐杰.妇产科学.第七版.北京.人民卫生出版社.2008:282-284.
[6]沈铿.复发性卵巢癌的诊断和治疗策略.现代妇产科进展.2005,5(14).177-180.
[7] F.Gieseler P,Rudolph G .KloeppelU,et al .Resistance mechanisms of ovarian cancers : why does conventional chemotheraphy fail ? Int J Colorectal Dis.2003,18:470-480.
[8]李同度.临床肿瘤学.安徽科学出版社.1992:48-50.
[9] Nurten Gunduz ,Beruard Fisher,Elizabeth A.Saffer. Effect of surgical Removal on the growth and Kinetics of Residual Tumor.CANCER research,1979,39:3861-3865.
[10]孙燕,汤钊猷等.UICC《临床肿瘤学手册》.第8版.人民卫生出版社,2006:455-457.
[11] Motoya T.Biological characterization including sensitivity to mitomycin C of culured human ovarian cancers.Nippon Sanka Fujinka Gakkai Zasshi.1981,33(8):119 7-2004.
[12] Matkman M,Reichman B,Hares T,et al..Intraperitoneal Chemotherapy in the Management of Ovarian Cancer.Cancer,1993,71(4):1565~1570.
[13]沈铿,郎景和,等.卵巢癌化疗的现状和展望.中华妇产科杂志.1994,29(12):755～756.
[14]连利娟.卵巢癌化疗的现状与趋向.中华妇产科杂志.1996,31(2):67～70.
[15]杨纪华.循环热灌注化疗治疗恶性腹腔积液疗效观察.西安.第四军医大学.2009.
[16]刘会波,王仁友等.间质化疗临床应用研究进展.中国肿瘤.2005,3(14):174-177.
[17]朱雯怡,范跃祖,阎波,等.结肠旁植入氟尿嘧啶缓释剂化疗的药代动力学实验研究.中国肿瘤, 2007; 16: 63-65.
[18]洪艳艳,陈振东,等.氟尿嘧啶植入剂治疗恶性胸腹水的药代动力学研究.中国临床药理学杂志.2009,7:298-301.
[19]王波.关于5-Fu应用者血压计药浓度监测的研究..实用肿瘤杂志.1993,8(3):185-187.
[20]李井泉,赵平,等.5-氟尿嘧啶缓释化疗药代动力学研究.中国全科医学. 2007.10:630-631.
[21]Tuxen MK,Soletormos G Dombernowsky P.Tumor markers in the management of patients with ovarian cancer.Cancer Treat Rev,1995.21(3):215-245.
[22] Colombo N ,Parma G,Boeeiolone L,et.a1.Medical therapy of advanced malignant epithelial tumors of the ovary.Forum(Genova),2000,10:323—332.
[1] Jemal A,Siegel R,Ward E,et a1.Cancer statistics,2006.[J].CA Cancer J Clin.2006,56(2):106—130.
[2] Bristow RE,Tomaoruz RS,Armstrong DK,et a1.Survival effect of maximal eytoreduetive surgery for advanced ovadan carcinoma during the platinum era:a meta—analysis.[J].J Clin Oncol.2002,20(5):1248—1259.
[3]颜萍,何畏.化疗对卵巢癌患者免疫功能的影响.重庆医学.2002,31(7):597—604.
[4] WeinbergBD,Ai H,Blanco E,et al.Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods[J]. Bioed Mater Res A,2007,81(1):161-70.
[5] Rapoport N.Combined cancer therapy by micellar - encapsulated drug and ultrasound.[J].Int J Pharm,2004,277(122):155-62.
[6] Rapoport N,Gao Z,KennedyA.Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy[J].J Natl Cancer Inst.2007,99(14):1095 -1106.
[7] Nasongkla N, Wiedmann AF, Bruening A,et al.Enhancement of solubility and bioavailability of beta-lapachone using cyclodextrin inclusion complexes[J].Pharm Res,2003,20(10):1626-1633.
[8] Kan P,Lin XZ,Hsieh MF,et al.Thermogelling emulsions for vascular embolization and sustained release of drugs.[J].Biomed Mater Res B Appl Biomater.2005,75(1):185-92.
[9] Blanco E,Qian F,Weinberg B,et al.Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers.[J].Biomed Mater Res A,2004,69(3):398-406.
[10] Sinha VR ,et al.Chitosan microspheres as a potential carrier for drugs.[J].Int J Pharm.2004,274(1-2)∶136-140.
[11] Ruel-Gariepy E,et al.A thermosensitive chitosan–based hydrogel for the local delivery of paclitaxel.[J].Eur J Pharm Biop-harm,2004, 57(1)∶153-162.
[12] Qian F,Stowe N,Liu EH,et al.Quantification of in vivo doxorubicin transport from PLGA millirods in thermoablated rat livers.[J].Control Release,2003,91(122):157-166.
[13] AhmedM,Liu Z,LukyanovAN,etal.Combination radiofrequency ablation with intratumoral liposomal doxorubicin:effect on drug accumulation and coagulation in multiple tissues and tumor types in animals.[J]. Radiology.2005,235(2):469-477.
[14] Vassileva V, Allen CJ,et al.Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer.[J].Mol Cancer Ther.2008;7(3):630-637.
[15] Vassileva V,Moriyama EH,et al.Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.[J].Br J Cancer.2008,99(12): 2037-2043.
[16] Lu Z,Tsai M,et al.Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer.[J].J Pharmacol Exp Ther. 2008,327(3):673-682.
[17]Vassileva V,Grant J,et al.Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model.[J].Cancer Chemother Pharmacol.2007,60(6):907-914.
[18]Lu H,Li B,et al.Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting.[J]. Cancer Chemother Pharmacol.2007 ,59(2):175-181.
[19]陈峥峥,凌斌等.5-Fu缓释剂局部埋植治疗卵巢癌腹膜后转移的实验研究.[J].安徽医科大学学报.2005,40(6):538-540.
[20]Armstrong DK,Fleming GF,et al.A phase I trial of intraperitoneal sustained-release paclitaxel microspheres(Paclimer) in recurrent ovarian cancer: aGynecologic Oncology Group study.[J].Gynecol Oncol. 2006,103(2):391-396.