• 1. 四川大學(xué)華西第二醫(yī)院婦產(chǎn)科（成都 610041）2. 四川大學(xué)華西醫(yī)院中國(guó)循證醫(yī)學(xué)中心;

目的 　評(píng)價(jià)托泊替康在復(fù)發(fā)性卵巢癌化療中的療效，安全性以及成本效果。
方法 　計(jì)算機(jī)檢索MEDLINE（1966～2005），EMbase（1974～2005）， CancerLit（1996～2003），中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫（1978～2005）。中國(guó)期刊全文數(shù)據(jù)庫（1994～2005），The Cochrane Central Register of Controlled Trials（CENTRAL），The National Research Register, Health Technology Assessment Database（HTA），Cochrane圖書館（2005年第3期）等數(shù)據(jù)庫。手工檢索相關(guān)領(lǐng)域的雜志，并用Google等搜索引擎在互聯(lián)網(wǎng)上查找相關(guān)的文獻(xiàn)。檢索截止至2005年12月。收集有關(guān)托泊替康（TPT）與其他藥物比較治療復(fù)發(fā)性卵巢癌（ROC）的隨機(jī)對(duì)照試驗(yàn)(RCT)文獻(xiàn)。由兩名研究者獨(dú)立評(píng)價(jià)納入研究的文獻(xiàn)質(zhì)量,并提取有效數(shù)據(jù)進(jìn)行Meta分析。
結(jié)果 　共納入4個(gè)RCT（9篇文獻(xiàn)，1 032例病人）。其中1個(gè)多中心RCT（474例，B級(jí)），比較TPT與脂質(zhì)體阿霉素（PLD）治療ROC的療效和成本；另1個(gè)多中心RCT（226例，A級(jí)），比較托泊替康與紫杉醇的療效。還有1個(gè)RCT（266例，B級(jí)）為TPT不同用藥途徑的比較；最后1個(gè)RCT（66例，A級(jí)）比較了TPT兩種用藥方案及劑量。結(jié)果顯示：① TPT與紫杉醇比較： 臨床受益率TPT大于紫杉醇，兩者差異有統(tǒng)計(jì)學(xué)意義；緩解率、疾病穩(wěn)定率的差異無統(tǒng)計(jì)學(xué)意義；3/4級(jí)血液學(xué)毒性TPT高于紫杉醇，對(duì)鉑類耐藥者TPT的生存時(shí)間長(zhǎng)于紫杉醇, 差異有統(tǒng)計(jì)學(xué)意義；兩者生存質(zhì)量差異無統(tǒng)計(jì)學(xué)意義。② TPT與PLD比較： 臨床受益率、緩解率差異無統(tǒng)計(jì)學(xué)意義。3/4級(jí)血液學(xué)毒性，TPT高于PLD，差異有統(tǒng)計(jì)學(xué)意義。對(duì)鉑類敏感者TPT組的生存時(shí)間短于PLD組： 1年生存率差異無統(tǒng)計(jì)學(xué)意義；2、3年生存率TPT低于PLD，差異有統(tǒng)計(jì)學(xué)意義。成本效果分析：TPT的治療總成本高于PLD；二者生活質(zhì)量差異無統(tǒng)計(jì)學(xué)意義。③ TPT兩種用藥劑量（方案）的比較：標(biāo)準(zhǔn)方案的緩解率及3/4級(jí)中性粒細(xì)胞減少的血液學(xué)毒性均大于24 h靜滴方案；生存時(shí)間差異無統(tǒng)計(jì)學(xué)意義。④ TPT口服與靜脈兩種用藥途徑相比：總緩解率靜脈途徑大于口服途徑；口服途徑的中性粒細(xì)胞減少的血液學(xué)毒性小于靜脈途徑，生存時(shí)間短于靜脈途徑。
結(jié)論 　在ROC的化療中，TPT的療效優(yōu)于紫杉醇，與PLD相當(dāng)（TPT的臨床受益率大于紫杉醇，緩解率相當(dāng)于紫杉醇，對(duì)鉑類耐藥ROC患者TPT治療的生存率大于紫杉醇）。TPT的緩解率和臨床受益率與PLD差異無統(tǒng)計(jì)學(xué)意義，TPT的2、3年生存率低于PLD，鉑類敏感的生存時(shí)間小于PLD；血液學(xué)毒性TPT大于紫杉醇和PLD；治療成本TPT高于PLD。關(guān)于TPT在ROC的二線化療中的臨床應(yīng)用，推薦用于耐藥性、難治性的卵巢癌，選用治療效果足夠、毒性可以耐受的5天靜脈滴注的標(biāo)準(zhǔn)治療方案。

引用本文： 裴海英,方 芳,田金徽,吳泰相. 托泊替康治療復(fù)發(fā)性卵巢癌的系統(tǒng)評(píng)價(jià). 中國(guó)循證醫(yī)學(xué)雜志, 2006, 06(10): 733-742. doi: 復(fù)制

1. Thigpena JT, Aghajanianb CA, Albertsc DS, et al. Role of pegylated liposomal doxorubicin in ovarian cancer. Gynecologic Oncology, 2005; 68(96): 10–18.
2. Latorre A, De Lena M, Catino A, et al. Epithelial ovarian cancer-second and third line chemotherapy (review). Int J Oncol, 2002; 21(6): 179–186.
3. Ozols R.F, Update on the management of ovarian cancer. Cancer, 2002; 8(suppl 1): S22–30.
4. Gadducci A, Sartore E, Maggino T, et al. Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian Multicenter study. Gynecol Oncol, 1998; 68(156): 150–155.
5. Swenerton K, Muss HB, Robinson EG. Salvage chemotherapy for refractory disease. In: Gershenson DM, McGuire WP: Ovarian cancer controversies on management. NY, Charchill livingstone, 1998: P169–194.
6. Parazzini F, Raspagliesi F, Guarnerio P, et al. Role of secondary surgery in relapsed ovarian cancer. Cri Rer Oncol Hematol, 2001; 32(25): 121–125.
7. Armstrong DK. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist, 2002; 7(suppl 5): 20–28.
8. National Institute for Clinical Excellence: Final Appraisal Determination. Ovarian cancer (advanced): topotecan, pegylated liposomal doxorubicin hydrochloridn and paclitaxel. NICE. March 2005.
9. Rustin GJS, Nelstrop ARE, McClean P, et al. Defining response of ovarian carcinoma to initial chemotherapy according to serum CA-125. Clin Oncol, 1996; 14(5): 1545–1551.
10. Rustin GJS, Nelstrop ARE, Crawford M, et al. Phase II trial of oral altretamine for relapsed ovarian carcinoma: Evaluation of defining response by serum CA-125. Clin Oncol, 1997; 15(1): 172–176.
11. Martin Gore, Wim ten Bokkel Huinink, James Carmichael, et al. Clinical Evidence for Topotecan-Paclitaxel Non-Cross-Resistance in Ovarian Cancer. Clin Oncol, 2001; 19(7): 1893–1900.
12. Gordon-AN, Fleagle-JT, Guthrie-D, et al. Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan. Clinical Oncology, 2001; 19(14): 3312–3322.
13. Smith DH, Adams JR, Johnston SR, et al. A comparative economic analysis of pegylated liposomal doxorubicin versus topotecan in ovarian cancer in the USA and the UK. Ann Oncol, 2002; 13(10):.
14. Cohen J: A coefficient of agreement for nominal scales. Educational and Psychological Measurement, 1960; 20(42): 37–46.
15. Moher D, Pham B, Jones A, et al. Does quality of reports of randomized trials affectestimates of intervention efficacy reported in meta-analyses. Lancet, 1998; 352(9128): 609–613.
16. Gordon AN,Tonda M,Sun S, et al. Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol, 2004; 95(1): 1–8.
17. Capri S, Cattaneo G. Cost-minimization analysis of pegylated liposomal doxorubicin versus topotecan for the treatment of ovarian cancer in Italy. Clin Ther, 2003; 25(6): 1826–1845.
18. Ojeda B, de Sande LM, Casado A, et al. Cost-minisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain. Br. J Cancer, 2003; 89(6): 1002–1007.
19. Ten Bokkel Huinink W, Lane SR, Ross GA, et al. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Annals of oncology, 2004; 15(1): 100–103.
20. Ten Bokkel Huinink W, Gore M, Carminchael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. Clinical Oncology, 1997; 15(6): 2183–2193.
21. Hoskins P, Eisenhauer E, Beare S, et al. Randomized Phase II Study of Two Schedules of Topotecan in Previously Treated Patients With Ovarian Cancer: A National Cancer Institute of Cancer Institute of Canada Clinical Trials Group Study. Clin Oncol, 1998; 16(6): 2233–2237.
22. M Gore, A Ozab, G Rustinc, et al. A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer. Eur. J Cancer, 2002; 38(32): 57–63.
23. Markman M, Kennedy A, Webster K, et al. Phase 2 evaluation of topotecan administered on a 3-days schedule in the treatment of platinum- and paclitaxel-refractory ovarian cancer. Gynecol Oncol, 2000; 7766: 116–119.
24. Levya T, Inbarb M, Menczera J, et al. Phase II study of weekly topotecan in patients with recurrent or persistent epithelial ovarian cancer. Gynecol Oncol, 2004; 95(186): 686–690.
25. Johnson S, Pyle l, King K, et al. A phase II study of topotecan given as a continuous 21-day infusion every 28 days in platinum pre-treated ovarian carcinoma. Eur J Cancer, 1997; 58(78): abstr 537.
26. –1597.
  1. 1. Thigpena JT, Aghajanianb CA, Albertsc DS, et al. Role of pegylated liposomal doxorubicin in ovarian cancer. Gynecologic Oncology, 2005; 68(96): 10–18.
  2. 2. Latorre A, De Lena M, Catino A, et al. Epithelial ovarian cancer-second and third line chemotherapy (review). Int J Oncol, 2002; 21(6): 179–186.
  3. 3. Ozols R.F, Update on the management of ovarian cancer. Cancer, 2002; 8(suppl 1): S22–30.
  4. 4. Gadducci A, Sartore E, Maggino T, et al. Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian Multicenter study. Gynecol Oncol, 1998; 68(156): 150–155.
  5. 5. Swenerton K, Muss HB, Robinson EG. Salvage chemotherapy for refractory disease. In: Gershenson DM, McGuire WP: Ovarian cancer controversies on management. NY, Charchill livingstone, 1998: P169–194.
  6. 6. Parazzini F, Raspagliesi F, Guarnerio P, et al. Role of secondary surgery in relapsed ovarian cancer. Cri Rer Oncol Hematol, 2001; 32(25): 121–125.
  7. 7. Armstrong DK. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist, 2002; 7(suppl 5): 20–28.
  8. 8. National Institute for Clinical Excellence: Final Appraisal Determination. Ovarian cancer (advanced): topotecan, pegylated liposomal doxorubicin hydrochloridn and paclitaxel. NICE. March 2005.
  9. 9. Rustin GJS, Nelstrop ARE, McClean P, et al. Defining response of ovarian carcinoma to initial chemotherapy according to serum CA-125. Clin Oncol, 1996; 14(5): 1545–1551.
  10. 10. Rustin GJS, Nelstrop ARE, Crawford M, et al. Phase II trial of oral altretamine for relapsed ovarian carcinoma: Evaluation of defining response by serum CA-125. Clin Oncol, 1997; 15(1): 172–176.
  11. 11. Martin Gore, Wim ten Bokkel Huinink, James Carmichael, et al. Clinical Evidence for Topotecan-Paclitaxel Non-Cross-Resistance in Ovarian Cancer. Clin Oncol, 2001; 19(7): 1893–1900.
  12. 12. Gordon-AN, Fleagle-JT, Guthrie-D, et al. Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan. Clinical Oncology, 2001; 19(14): 3312–3322.
  13. 13. Smith DH, Adams JR, Johnston SR, et al. A comparative economic analysis of pegylated liposomal doxorubicin versus topotecan in ovarian cancer in the USA and the UK. Ann Oncol, 2002; 13(10):.
  14. 14. Cohen J: A coefficient of agreement for nominal scales. Educational and Psychological Measurement, 1960; 20(42): 37–46.
  15. 15. Moher D, Pham B, Jones A, et al. Does quality of reports of randomized trials affectestimates of intervention efficacy reported in meta-analyses. Lancet, 1998; 352(9128): 609–613.
  16. 16. Gordon AN,Tonda M,Sun S, et al. Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol, 2004; 95(1): 1–8.
  17. 17. Capri S, Cattaneo G. Cost-minimization analysis of pegylated liposomal doxorubicin versus topotecan for the treatment of ovarian cancer in Italy. Clin Ther, 2003; 25(6): 1826–1845.
  18. 18. Ojeda B, de Sande LM, Casado A, et al. Cost-minisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain. Br. J Cancer, 2003; 89(6): 1002–1007.
  19. 19. Ten Bokkel Huinink W, Lane SR, Ross GA, et al. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Annals of oncology, 2004; 15(1): 100–103.
  20. 20. Ten Bokkel Huinink W, Gore M, Carminchael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. Clinical Oncology, 1997; 15(6): 2183–2193.
  21. 21. Hoskins P, Eisenhauer E, Beare S, et al. Randomized Phase II Study of Two Schedules of Topotecan in Previously Treated Patients With Ovarian Cancer: A National Cancer Institute of Cancer Institute of Canada Clinical Trials Group Study. Clin Oncol, 1998; 16(6): 2233–2237.
  22. 22. M Gore, A Ozab, G Rustinc, et al. A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer. Eur. J Cancer, 2002; 38(32): 57–63.
  23. 23. Markman M, Kennedy A, Webster K, et al. Phase 2 evaluation of topotecan administered on a 3-days schedule in the treatment of platinum- and paclitaxel-refractory ovarian cancer. Gynecol Oncol, 2000; 7766: 116–119.
  24. 24. Levya T, Inbarb M, Menczera J, et al. Phase II study of weekly topotecan in patients with recurrent or persistent epithelial ovarian cancer. Gynecol Oncol, 2004; 95(186): 686–690.
  25. 25. Johnson S, Pyle l, King K, et al. A phase II study of topotecan given as a continuous 21-day infusion every 28 days in platinum pre-treated ovarian carcinoma. Eur J Cancer, 1997; 58(78): abstr 537.
  26. 26. –1597.