Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer

  • Su, An (Department of Medical Oncology, Zhongshan Hospital of Xiamen University) ;
  • Zhang, Jing (Department of Hematological Oncology, Cancer Center of Sun-Yat Sen University) ;
  • Pan, Zhan-He (Department of Medical Oncology, Zhongshan Hospital of Xiamen University) ;
  • Zhou, Qi-Ming (Department of Medical Oncology, Nanshan District Hospital of Shenzhen) ;
  • Lv, Xia (Department of Medical Oncology, Zhongshan Hospital of Xiamen University)
  • Published : 2013.03.30


Anti-angiogenic agents have played crucial roles in the treatment of ovarian cancer in recent years, but potential benefits of endostatin have been largely unexplored. The present retrospective study evaluated its efficacy and toxicity with two cohorts of patients with platinum-resistant recurrent ovarian cancer. One cohort received gemcitabine plus endostar (rh-endostatin), and the second cohort received gemcitabine regimen alone, with totals of 31 and 27 patients, respectively. The main endpoints were disease control rate (DCR), PFS, overall survival (OS) and safety. There were statistically significant differences in DCR (70.9% vs. 40.7%; P = 0.02) and PFS (6.3 months vs. 3.2 months, P = 0.001) between the two cohorts. Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case (12.5 months vs. 10.4 months, P = 0.201). Treatment was well tolerated for most patients, and toxicity of endostar was negligible. Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion. The endostar-containing regimen is recommended in this setting.


  1. Therasse P, Arbuck SG, Eisenhauer EA, et al (2000). 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 Natl Cancer Inst, 92, 205-16.
  2. Wang J, Sun Y, Liu Y, et al (2005). [Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients.]. Zhongguo Fei Ai Za Zhi, 8, 283-90.
  3. Wickstrom SA, Alitalo K, Keski-Oja J (2002). Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res, 62, 5580-9.
  4. Winter WE, 3rd, Maxwell GL, Tian C, et al (2007). Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol, 25, 3621-7.
  5. Wu G, Zhang R, Ren J, Sun Y (2008). Autophagic cell death of human hepatoma cells induced by endostar, a recombinant human endostatin. Cancer Biother Radiopharm, 23, 735-40.
  6. Yokoyama Y, Sedgewick G, Ramakrishnan S (2007). Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination. Cancer Res, 67, 10813-22.
  7. Zebrowski BK, Liu W, Ramirez K, et al (1999). Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol, 6, 373-8.
  8. Zhou JF, Bai CM, Wang, YZ, et al (2011a). Endostar combined with chemotherapy for treatment of metastatic colorectal and gastric cancer: a pilot study. Chin Med J (Engl), 124, 4299-303.
  9. Zhou N, Hu G, Mei Q, et al (2011b). Inhibitory effect of endostar in combination with radiotherapy in a mouse model of human CNE2 nasopharyngeal carcinoma. J Huazhong Univ Sci Technolog Med Sci, 31, 62-6.
  10. Aghajanian C, Blank SV, Goff BA, et al (2012). OCEANS:a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol, 30, 2039-45.
  11. Burger RA, Brady MF, Bookman MA, et al (2011). Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med, 365, 2473-83.
  12. Byrne AT, Ross L, Holash J, et al (2003). Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res, 9, 5721-8.
  13. Ferrandina G, Ludovisi M, Lorusso D, et al (2008). Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol, 26, 890-6.
  14. Fu Y, Tang H, Huang Y, Song N, Luo Y (2009). Unraveling the mysteries of endostatin. IUBMB Life, 61, 613-26.
  15. Hamilton CA, Maxwell GL, Chernofsky MR, et al (2008). Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer. Gynecol Oncol, 111, 530-2.
  16. Han B, Xiu Q, Wang H, et al (2011). A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of paclitaxel-carboplatin alone or with endostar for advanced non-small cell lung cancer. J Thorac Oncol, 6, 1104-9.
  17. Hartenbach EM, Olson TA, Goswitz JJ, et al (1997). Vascular endothelial growth factor (VEGF) expression and survival in human epithelial ovarian carcinomas. Cancer Lett, 121, 169-75.
  18. Ke QH, Zhou SQ, Huang M, et al (2012). Early efficacy of Endostar combined with chemoradiotherapy for advanced cervical cancers. Asian Pac J Cancer Prev, 13, 923-6.
  19. O'Reilly MS, Boehm T, Shing Y, et al (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88, 277-85.
  20. Ozols RF, Bundy BN, Greer BE, et al (2003). Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol, 21, 3194-200.
  21. Paley PJ, Staskus KA, Gebhard K, et al (1997). Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer, 80, 98-106.<98::AID-CNCR13>3.0.CO;2-A
  22. Perren TJ, Swart AM, Pfisterer J, et al (2011). A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med, 365, 2484-96.
  23. Roland PY, Barnes MN, Niwas S, et al (1998). Response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel and platinum-based combination regimens. Gynecol Oncol, 68, 178-82.
  24. Rose PG, Blessing JA, Mayer AR, Homesley HD (1998). Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol, 16, 405-10.

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