喜樹堿類衍生物在卵巢癌治療中的進展_《華西醫學》

作者：

賈月改 ,  樓江燕

四川大學華西第二醫院婦產科（成都，610041）;

關鍵詞：

喜樹堿喜樹堿類衍生物拓撲異構酶I 卵巢癌

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

喜樹堿類衍生物是一類具有抗癌活性的生物堿，通過抑制拓撲異構酶I而產生抗腫瘤作用。目前大量臨床研究表明，喜樹堿及其衍生物對卵巢癌，尤其是對鉑類藥物化學治療失敗、復發的卵巢癌有較好療效。現將喜樹堿類衍生物在卵巢癌治療中的研究進展作一綜述。

引用本文： 賈月改,樓江燕. 喜樹堿類衍生物在卵巢癌治療中的進展. 華西醫學, 2012, 27(4): 617-621. doi: 復制

1.	沈鏗, 郎景和. 卵巢上皮癌診斷和治療中應注意的問題[J]. 中華婦產科雜志, 2003, 38 (3): 65- 68.
2.	王薇, 馬丁. 拓撲替康在卵巢癌治療中的新進展[J]. 國外醫學婦幼保健分冊, 2003, 14(6): 1008-2514.
3.	Wall ME, Wani MC, Cooke CE, et al. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumour inhibitor from camptotheca acuminate[J]. J Am Chem Soc, 1966, 88(16): 3888-3890.
4.	Legarza K, Yang L-X. Novel camptothecin derivatives[J]. J In Vivo, 2005, 19(1): 283-293.
5.	Eng W-K, Faucette L, Johnson RK, et al. Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin[J]. Mol Pharmacol, 1988, 34(6): 755-760.
6.	Tse YC, Kirkegaard K, Wang JC. Covalent bonds between protein and DNA. Formation of phosphotyrosine linkage between certain DNA topoisomerases and DNA[J]. J Biol Chem, 1980, 255(12): 5560-5565.
7.	Morris EJ, Geller HM. Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase I: evidence for cell cycle-independent toxicity[J]. J Cell Biol, 1996, 134(3): 757-70.
8.	Wu J, Yin M-B, Hapke G, et al. Induction of biphasic DNA double strand breaks and activation of multiple repair protein complexes by DNA topoisomerase I drug 7-ethyl-10-hydroxy-camptothecin[J]. Mol Pharmocol, 2002, 61(4): 742-748.
9.	Collins I, Weber A, Levens D, et al. Transcriptional consequences of topoisomerase inhibition[J]. Mol Cell Biol, 2001, 21(24): 8437-8451.
10.	Mosesso P, Pichierri P, Franchiitto A, et al. Evidence that camptothecin-induced aberrations in the G(2) phase of cell cycle of Chinese hamster ovary (CHO) cell lines is associated with transcription[J]. Mutat Res 2000, 452(2): 189-195.
11.	Hayward RL, Macpherson JS, Cummings J, et al. Antisense Bcl-xl down-regulation switches the response to topoisomerase I inhibition from senescence to apoptosis in colorectal cancer cells, enhancing global cytotoxicity[J]. J Clin Cancer Res , 2003, 9(7): 2856-2865.
12.	Ullmannova V, Haskovec C. Gene expression during camptothecin-induced apoptosis in human myeloid leukemia cell line ML-2[J]. Neoplasma , 2004, 51(3): 175-180.
13.	Huang TT, Wuerzberger-Davis SM, Seufzer BJ, et al. NF-kappaB activation by camptothecin. A linkage between nuclear DNA damage and cytoplasmic signaling events[J]. J Biol Chem, 2000, 275(13): 9501-9509.
14.	Carson JP, Zhang N, Frampton GM, et al. Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin[J]. Cancer Res , 2004, 64(6): 2096-2104.
15.	Flatten K, Dai NT, Vroman BT, et al. The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons[J]. J Biol Chem, 2005, 280(14): 14349-14355.
16.	Wang H, Wang X, Shou X-Y, Ku, et al. Ku affects the ataxia and Rad 3-related/CHK1-dependent S phase checkpoint response after camptothecin treatment[J]. Cancer Res, 2002, 62(9): 2483-2487.
17.	Furuta T, Takemura H, Liao Z-Y, et al. Phosphorylation of histone H2AX and activation of Mre11,Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNAtopoisomerase I cleavage complexes[J]. J Biol Chem, 2003, 278(22): 20303-20312.
18.	Adachi N, So S, Koyama H. Loss of nonhomologous end joining confers comptothecin resistance in DT40 cells. Implications for the repair of topoisomerase I-mediated DNA damage[J]. J Biol Chem, 2004, 279(36): 37343-37348.
19.	Mariadason JM, Arango D, Shi Q, et al. Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin[J]. Cancer Res, 2003, 63(24): 8791-8812.
20.	Jiang Q, Wang Hx. Research and Application of Camptothecins [J] . Prog Pharm Sci, 2007, 31(9): 408- 412.
21.	Rowinsky EK, Grochow LB, Bendricks CB, et al. Phase I and pharmacologic study of topotacan: a novel topoisomerase I inhibitor[J]. J Clin Oncol, 1992, 10(4): 647 -656.
22.	Kudelka Ap, Tres ukos ol D, Edwards Cl, et al. A Phase Ⅱ study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma[J]. J Clin Oncol, 1996, 14(5): 1552 -1557.
23.	Gore M, Carmichael J, Gordon A, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer[J]. J Clin Oncol, 1997, 15(6): 2183- 2193.
24.	Sehouli J, Stengel D,Oskay-Oezcelik G, et al. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phaseⅢ study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group[J]. J Clin Oncol, 2008, 26(19): 3176-3182.
25.	Gore M, ten Bokkel Huinink W, Carmichael J, et al. Clinical evidence for topotecan paclitaxel noncross-resistance in ovarian cancer [J]. J Clin On col , 2001, 19(7): 1893-1900.
26.	Coleman R L. Emerging role of topotecan in front line treatment of carcinoma of the ovary [J]. The On cologist, 2002, 7 ( S5) : 46-55.
27.	Vecchione F, Fruscio R, Dell’Anna T, et al. A phaseⅡ clinical trial of topotecan and carboplatin in patients with newly diagnosed advanced epithelial ovarian cancer[J]. Int J Gynecol Cancer, 2007, 17(2): 367-372.
28.	Morris R, Munkarah A. Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer [J] . The Oncologist , 2002, 7(S5) : 29- 35.
29.	Largillier R, Valenza B, Ferrero JM, et al. Haematological evaluation of weekly therapy with topotecan for the treatment of recurrent ovarian cancer resistant to platinum-based therapy[J]. Oncology, 2007, 73(3-4): 177-184.
30.	Möbus V, Kieback DG, Kaubitzsch SK. Duration of chemotherapy with topotecan influences survival in recurrent ovarian cancer: a meta-analysis[J]. Anticancer Res, 2007, 27(3B): 1581-1587.
31.	Calcagno M, Bellati F, Palaia I, et al. Three-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients[J]. Int J Gynecol Cancer, 2009, 19(3): 455-459.
32.	Comander AH, Cannistra SA. A feasibility study of low-dose, prolonged oral topotecan in patients with advanced ovarian, fallopian tube, or primary peritoneal serous cancer who have attained a complete clinical response following platinum-based chemotherapy[J]. Int J Gynecol Cancer, 2008, 18(1):51-58.
33.	Muntz HG, Malpass TW, McGonigle KF, et al. Phase 2 study of intraperitoneal topotecan as consolidation chemotherapy in ovarian and primary peritoneal carcinoma[J]. Cancer, 2008,113(3): 490-496.
34.	Sugiyama T, Yakushiji M, Ochiai K, et al. Japanese ovarian trials: focus on irinotecan[J]. Oncology (Williston Park), 2003, 17(Suppl 5): 29-33.
35.	Takano M, Sugiyama T, Yaegashi N, et al. Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis[J]. Int J Clin Oncol, 2007, 12(4): 256-260.
36.	Takakura S, Saito M, Ueda K., et al. Irinotecan hydrochloride (CPT-11) and cisplatin as first-line chemotherapy after initial surgery for ovarian clear cell adenocarcinoma[J]. Int Surg, 2007, 92(4): 202-208.
37.	Nishino K, Aoki Y, Amikura T, et al. Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma[J]. Gynecol Oncol, 2005, 97(3): 893-897.
38.	Hirakawa H, Futagami M, Yokoyama Y, et al. Successful optimal debulking surgery following chemotherapy combined with irinotecan hydrochloride and cisplatin for advanced clear cell carcinoma of the ovary[J]. Gan To Kagaku Ryoho, 2011, 38(5): 857-860.
39.	Taylor J, Amanze A, Di Federico E, et al. Irinotecan use during pregnancy[J]. Obstet Gynecol, 2009, 114(2): 451-452.
40.	Wang L Y. AntineoplasticI irinotecan research progress [J]. Foreign Med Sci (SecPharm), 2004, 31 (1): 71.
41.	Matsumoto K, Katsumata N, Yamanaka Y, et al. The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer[J]. Gynecol Oncol, 2006, 100(2): 412-416.
42.	Aoki Y, Kurata H., Watanabe M, et al. Combination chemotherapy with irinotecan hydrochloride (CPT-11) and mitomycin C in platinum-refractory ovarian cancer[J]. Am J Clin Oncol, 2004, 27(5): 461-464.
43.	Hong Mh, Pei Yy. Hydroxycamptothecin and for mulations [J]. Chin J ClinPharm, 2008, 17(4): 255-258.
44.	于榮,柳慶玲. 羥基喜樹堿腹腔灌注治療卵巢癌腹水24例[J]. 菏澤醫學專科學校學報, 2006, 18(1): 13.
45.	Li ZY, Guo Y. Camptothecinderi vatives a kind of antitum oragents [J] . Chin New Drugs J, 2000, 9(9): 598-601.
46.	魏林. 奧沙利鉑聯合羥喜樹堿治療復發性卵巢上皮癌應用研究[J]. 中國民族民間醫藥, 2010, 12(23): 1007-8517.
47.	徐瑛，周彩存，張捷. 羥基喜樹堿聯合異環磷酰胺治療鉑類耐藥的非小細胞肺癌的臨床研究[J]. 中國肺癌雜志, 2005, 8(1): 45- 47.
48.	Lee HP, Seo SS, Ryu SY, et al, PhaseⅡ evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or resistant ovarian cancer[J]. Gynecol Oncol, 2008, 109(3): 359-363.
49.	Nam EJ, Kim JW, Kim JH, et al. Efficacy and toxicity of belotecan with and without cisplatin in patients with recurrent ovarian cancer[J]. Am J Clin Oncol, 2010, 33(3): 233-237.
50.	Hee-Jung Ban, In-Jae oh, Kyu-Sik Kim, et al. Clinical efficacy of belotecan(CKD-602), newly developed camptothecin analog, in the 2nd line treatment of relapsed small cell lung cancer[J]. Tuberc Respir Dis, 2009, 66(2): 93-97.
51.	Kim HS, Park NH, Kang S, et al. Comparison of the efficacy between topotecan- and belotecan-, a new camptothecin analog, based chemotherapies for recurrent epithelial ovarian cancer: a single institutional experience[J]. J Obstet Gynaecol Res, 2010, 36(1): 86-93.
52.	Global Data. Karenitecin (Ovarian Cancer)- Analysis and Forecasts to 2020[DB/OL](2011-10-20)[2012-3-31]. http://www.pharmaceutical-market-research.com/publications/therapeutic/karenitecin_ovarian_cancer_analysis_forecast_2020.html.
53.	Kavanagh J, Sill MW, Ramirez PT, et al. PhaseⅡ multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study[J]. Int J Gynecol Cancer, 2008, 18(3): 460-464.
54.	Pecorelli S, Ray-Coquard I, Tredan O, et al. PhaseⅡ of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes[J]. Ann Oncol, 2010, 21(4): 759-765.

1. 　沈鏗, 郎景和. 卵巢上皮癌診斷和治療中應注意的問題[J]. 中華婦產科雜志, 2003, 38 (3): 65- 68.
2. 　王薇, 馬丁. 拓撲替康在卵巢癌治療中的新進展[J]. 國外醫學婦幼保健分冊, 2003, 14(6): 1008-2514.
3. 　Wall ME, Wani MC, Cooke CE, et al. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumour inhibitor from camptotheca acuminate[J]. J Am Chem Soc, 1966, 88(16): 3888-3890.
4. 　Legarza K, Yang L-X. Novel camptothecin derivatives[J]. J In Vivo, 2005, 19(1): 283-293.
5. 　Eng W-K, Faucette L, Johnson RK, et al. Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin[J]. Mol Pharmacol, 1988, 34(6): 755-760.
6. 　Tse YC, Kirkegaard K, Wang JC. Covalent bonds between protein and DNA. Formation of phosphotyrosine linkage between certain DNA topoisomerases and DNA[J]. J Biol Chem, 1980, 255(12): 5560-5565.
7. 　Morris EJ, Geller HM. Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase I: evidence for cell cycle-independent toxicity[J]. J Cell Biol, 1996, 134(3): 757-70.
8. 　Wu J, Yin M-B, Hapke G, et al. Induction of biphasic DNA double strand breaks and activation of multiple repair protein complexes by DNA topoisomerase I drug 7-ethyl-10-hydroxy-camptothecin[J]. Mol Pharmocol, 2002, 61(4): 742-748.
9. 　Collins I, Weber A, Levens D, et al. Transcriptional consequences of topoisomerase inhibition[J]. Mol Cell Biol, 2001, 21(24): 8437-8451.
10. 　Mosesso P, Pichierri P, Franchiitto A, et al. Evidence that camptothecin-induced aberrations in the G(2) phase of cell cycle of Chinese hamster ovary (CHO) cell lines is associated with transcription[J]. Mutat Res 2000, 452(2): 189-195.
11. 　Hayward RL, Macpherson JS, Cummings J, et al. Antisense Bcl-xl down-regulation switches the response to topoisomerase I inhibition from senescence to apoptosis in colorectal cancer cells, enhancing global cytotoxicity[J]. J Clin Cancer Res , 2003, 9(7): 2856-2865.
12. 　Ullmannova V, Haskovec C. Gene expression during camptothecin-induced apoptosis in human myeloid leukemia cell line ML-2[J]. Neoplasma , 2004, 51(3): 175-180.
13. 　Huang TT, Wuerzberger-Davis SM, Seufzer BJ, et al. NF-kappaB activation by camptothecin. A linkage between nuclear DNA damage and cytoplasmic signaling events[J]. J Biol Chem, 2000, 275(13): 9501-9509.
14. 　Carson JP, Zhang N, Frampton GM, et al. Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin[J]. Cancer Res , 2004, 64(6): 2096-2104.
15. 　Flatten K, Dai NT, Vroman BT, et al. The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons[J]. J Biol Chem, 2005, 280(14): 14349-14355.
16. 　Wang H, Wang X, Shou X-Y, Ku, et al. Ku affects the ataxia and Rad 3-related/CHK1-dependent S phase checkpoint response after camptothecin treatment[J]. Cancer Res, 2002, 62(9): 2483-2487.
17. 　Furuta T, Takemura H, Liao Z-Y, et al. Phosphorylation of histone H2AX and activation of Mre11,Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNAtopoisomerase I cleavage complexes[J]. J Biol Chem, 2003, 278(22): 20303-20312.
18. 　Adachi N, So S, Koyama H. Loss of nonhomologous end joining confers comptothecin resistance in DT40 cells. Implications for the repair of topoisomerase I-mediated DNA damage[J]. J Biol Chem, 2004, 279(36): 37343-37348.
19. 　Mariadason JM, Arango D, Shi Q, et al. Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin[J]. Cancer Res, 2003, 63(24): 8791-8812.
20. 　Jiang Q, Wang Hx. Research and Application of Camptothecins [J] . Prog Pharm Sci, 2007, 31(9): 408- 412.
21. 　Rowinsky EK, Grochow LB, Bendricks CB, et al. Phase I and pharmacologic study of topotacan: a novel topoisomerase I inhibitor[J]. J Clin Oncol, 1992, 10(4): 647 -656.
22. 　Kudelka Ap, Tres ukos ol D, Edwards Cl, et al. A Phase Ⅱ study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma[J]. J Clin Oncol, 1996, 14(5): 1552 -1557.
23. 　Gore M, Carmichael J, Gordon A, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer[J]. J Clin Oncol, 1997, 15(6): 2183- 2193.
24. 　Sehouli J, Stengel D,Oskay-Oezcelik G, et al. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phaseⅢ study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group[J]. J Clin Oncol, 2008, 26(19): 3176-3182.
25. 　Gore M, ten Bokkel Huinink W, Carmichael J, et al. Clinical evidence for topotecan paclitaxel noncross-resistance in ovarian cancer [J]. J Clin On col , 2001, 19(7): 1893-1900.
26. 　Coleman R L. Emerging role of topotecan in front line treatment of carcinoma of the ovary [J]. The On cologist, 2002, 7 ( S5) : 46-55.
27. 　Vecchione F, Fruscio R, Dell’Anna T, et al. A phaseⅡ clinical trial of topotecan and carboplatin in patients with newly diagnosed advanced epithelial ovarian cancer[J]. Int J Gynecol Cancer, 2007, 17(2): 367-372.
28. 　Morris R, Munkarah A. Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer [J] . The Oncologist , 2002, 7(S5) : 29- 35.
29. 　Largillier R, Valenza B, Ferrero JM, et al. Haematological evaluation of weekly therapy with topotecan for the treatment of recurrent ovarian cancer resistant to platinum-based therapy[J]. Oncology, 2007, 73(3-4): 177-184.
30. 　Möbus V, Kieback DG, Kaubitzsch SK. Duration of chemotherapy with topotecan influences survival in recurrent ovarian cancer: a meta-analysis[J]. Anticancer Res, 2007, 27(3B): 1581-1587.
31. 　Calcagno M, Bellati F, Palaia I, et al. Three-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients[J]. Int J Gynecol Cancer, 2009, 19(3): 455-459.
32. 　Comander AH, Cannistra SA. A feasibility study of low-dose, prolonged oral topotecan in patients with advanced ovarian, fallopian tube, or primary peritoneal serous cancer who have attained a complete clinical response following platinum-based chemotherapy[J]. Int J Gynecol Cancer, 2008, 18(1):51-58.
33. 　Muntz HG, Malpass TW, McGonigle KF, et al. Phase 2 study of intraperitoneal topotecan as consolidation chemotherapy in ovarian and primary peritoneal carcinoma[J]. Cancer, 2008,113(3): 490-496.
34. 　Sugiyama T, Yakushiji M, Ochiai K, et al. Japanese ovarian trials: focus on irinotecan[J]. Oncology (Williston Park), 2003, 17(Suppl 5): 29-33.
35. 　Takano M, Sugiyama T, Yaegashi N, et al. Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis[J]. Int J Clin Oncol, 2007, 12(4): 256-260.
36. 　Takakura S, Saito M, Ueda K., et al. Irinotecan hydrochloride (CPT-11) and cisplatin as first-line chemotherapy after initial surgery for ovarian clear cell adenocarcinoma[J]. Int Surg, 2007, 92(4): 202-208.
37. 　Nishino K, Aoki Y, Amikura T, et al. Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma[J]. Gynecol Oncol, 2005, 97(3): 893-897.
38. 　Hirakawa H, Futagami M, Yokoyama Y, et al. Successful optimal debulking surgery following chemotherapy combined with irinotecan hydrochloride and cisplatin for advanced clear cell carcinoma of the ovary[J]. Gan To Kagaku Ryoho, 2011, 38(5): 857-860.
39. 　Taylor J, Amanze A, Di Federico E, et al. Irinotecan use during pregnancy[J]. Obstet Gynecol, 2009, 114(2): 451-452.
40. 　Wang L Y. AntineoplasticI irinotecan research progress [J]. Foreign Med Sci (SecPharm), 2004, 31 (1): 71.
41. 　Matsumoto K, Katsumata N, Yamanaka Y, et al. The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer[J]. Gynecol Oncol, 2006, 100(2): 412-416.
42. 　Aoki Y, Kurata H., Watanabe M, et al. Combination chemotherapy with irinotecan hydrochloride (CPT-11) and mitomycin C in platinum-refractory ovarian cancer[J]. Am J Clin Oncol, 2004, 27(5): 461-464.
43. 　Hong Mh, Pei Yy. Hydroxycamptothecin and for mulations [J]. Chin J ClinPharm, 2008, 17(4): 255-258.
44. 　于榮,柳慶玲. 羥基喜樹堿腹腔灌注治療卵巢癌腹水24例[J]. 菏澤醫學專科學校學報, 2006, 18(1): 13.
45. 　Li ZY, Guo Y. Camptothecinderi vatives a kind of antitum oragents [J] . Chin New Drugs J, 2000, 9(9): 598-601.
46. 　魏林. 奧沙利鉑聯合羥喜樹堿治療復發性卵巢上皮癌應用研究[J]. 中國民族民間醫藥, 2010, 12(23): 1007-8517.
47. 　徐瑛，周彩存，張捷. 羥基喜樹堿聯合異環磷酰胺治療鉑類耐藥的非小細胞肺癌的臨床研究[J]. 中國肺癌雜志, 2005, 8(1): 45- 47.
48. 　Lee HP, Seo SS, Ryu SY, et al, PhaseⅡ evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or resistant ovarian cancer[J]. Gynecol Oncol, 2008, 109(3): 359-363.
49. 　Nam EJ, Kim JW, Kim JH, et al. Efficacy and toxicity of belotecan with and without cisplatin in patients with recurrent ovarian cancer[J]. Am J Clin Oncol, 2010, 33(3): 233-237.
50. 　Hee-Jung Ban, In-Jae oh, Kyu-Sik Kim, et al. Clinical efficacy of belotecan(CKD-602), newly developed camptothecin analog, in the 2nd line treatment of relapsed small cell lung cancer[J]. Tuberc Respir Dis, 2009, 66(2): 93-97.
51. 　Kim HS, Park NH, Kang S, et al. Comparison of the efficacy between topotecan- and belotecan-, a new camptothecin analog, based chemotherapies for recurrent epithelial ovarian cancer: a single institutional experience[J]. J Obstet Gynaecol Res, 2010, 36(1): 86-93.
52. 　Global Data. Karenitecin (Ovarian Cancer)- Analysis and Forecasts to 2020[DB/OL](2011-10-20)[2012-3-31]. http://www.pharmaceutical-market-research.com/publications/therapeutic/karenitecin_ovarian_cancer_analysis_forecast_2020.html.
53. 　Kavanagh J, Sill MW, Ramirez PT, et al. PhaseⅡ multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study[J]. Int J Gynecol Cancer, 2008, 18(3): 460-464.
54. 　Pecorelli S, Ray-Coquard I, Tredan O, et al. PhaseⅡ of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes[J]. Ann Oncol, 2010, 21(4): 759-765.

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喜樹堿類衍生物在卵巢癌治療中的進展

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