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Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

  • Chanpanitkitchot, Saranya (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University) ;
  • Tangjitgamol, Siriwan (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University) ;
  • Khunnarong, Jakkapan (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University) ;
  • Thavaramara, Thaowalai (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University) ;
  • Pataradool, Kamol (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University) ;
  • Srijaipracharoen, Sunamchok (Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University)
  • Published : 2014.07.15

Abstract

Background: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. Materials and Methods: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. Results: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinum-sensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. Conclusions: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.

References

  1. Berek JS, Friedlander M, Hacker NF (2010). Epithelial ovarian, fallopian tube, and peritoneal cancer. In: Berek JS, Friedlander M, Hacker NF (eds) Berek & Hacker's Gynecologic oncology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 484-508.
  2. Bozas G, Bamias A, Koutsoukou V, et al (2007). Biweekly gemcitabine and cisplatin in platinum-resistant/refractory, paclitaxel-pretreated, ovarian and peritoneal carcinoma. Gynecol Oncol, 104, 580-5. https://doi.org/10.1016/j.ygyno.2006.09.006
  3. Brewer CA, Blessing JA, Nagourney RA, Morgan M, Hanjani P (2006). Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal cancer: a phase II study of the gynecologic oncology group. Gynecol Oncol, 103, 446-50. https://doi.org/10.1016/j.ygyno.2006.03.018
  4. D'Agostino G1, Amant F, Berteloot P, Scambia G, Vergote I (2003). Phase II study of gemcitabine in recurrent platinum-and paclitaxel-resistant ovarian cancer. Gynecol Oncol, 88, 266-9. https://doi.org/10.1016/S0090-8258(03)00011-8
  5. Ferlay J, Soerjomataram I, Ervik M, et al (2014). GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012.
  6. 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. https://doi.org/10.1200/JCO.2007.13.6606
  7. Ferrandina G, Paris I, Ludovisi M, et al (2005). Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol, 98, 267-73. https://doi.org/10.1016/j.ygyno.2005.04.018
  8. Friedlander M, Millward MJ, Bell D, et al (1998). A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer. Ann Oncol, 12, 1343-5.
  9. Garcia AA, O'Meara A, Bahador A, et al (2004). Phase II study of gemcitabine and weekly paclitaxel in recurrent platinum-resistant ovarian cancer. Gynecol Oncol, 93, 493-8. https://doi.org/10.1016/j.ygyno.2004.02.007
  10. Greggi S, Salerno MG, D'Agostino G, et al (2001). Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer. Oncology, 60, 19-23. https://doi.org/10.1159/000055291
  11. Karaoglu A, Arslan UY, Ozkan M, et al (2009). Efficacy and toxicity of gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer. Asian Pac J Cancer Prev, 10, 63-6.
  12. Khemapech N, Oranratanaphan S, Termrungruanglert W, Lertkhachonsuk R, Vasurattana A (2013). Salvage chemotherapy in recurrent platinum-resistant or refractory epithelial ovarian cancer with carboplatin and distearoylphosphatidylcholine pegylated liposomal doxorubicin (lipo-$dox^{(R)}$). Asian Pac J Cancer Prev, 14, 2131-5. https://doi.org/10.7314/APJCP.2013.14.3.2131
  13. Kucukoner M, Isikdogan A, Yaman S, et al (2012). Oral etoposide for platinum-resistant and recurrent epithelial ovarian cancer: a study by the anatolian society of medical oncology. Asian Pac J Cancer Prev, 13, 3973-6. https://doi.org/10.7314/APJCP.2012.13.8.3973
  14. Markman M, Webster K, Zanotti K, et al (2003). Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer. Gynecol Oncol, 90, 593-6. https://doi.org/10.1016/S0090-8258(03)00399-8
  15. Moore MA, Attasara P, Khuhaprema T, et al (2010). Cancer epidemiology in mainland South-East Asia - past, present and future. Asian Pac J Cancer Prev, 11 Epidemiology Suppl, 67-80.
  16. Mutch DG, Orlando M, Goss T, et al (2007). Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol, 25, 2811-8. https://doi.org/10.1200/JCO.2006.09.6735
  17. Nagourney RA, Brewer CA, Radecki S, et al (2003). Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients. Gynecol Oncol, 88, 35-9. https://doi.org/10.1006/gyno.2002.6855
  18. 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. https://doi.org/10.1200/JCO.2003.02.153
  19. Papadimitriou CA, Fountzilas G, Aravantinos G, et al (2004). Second-line chemotherapy with gemcitabine and carboplatin in paclitaxel-pretreated, platinum-sensitive ovarian cancer patients. A hellenic cooperative oncology group study. Gynecol Oncol, 92, 152-9. https://doi.org/10.1016/j.ygyno.2003.09.021
  20. Parmar MK, Ledermann JA, Colombo N, et al (2003). Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet, 361, 2099-106. https://doi.org/10.1016/S0140-6736(03)13718-X
  21. Pfisterer J, Plante M, Vergote I, et al (2006). Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol, 24, 4699-707. https://doi.org/10.1200/JCO.2006.06.0913
  22. Pitakkarnkul S, Tangjitgamol S, Srijaipracharoen S, et al (2013). Treatment outcomes of paclitaxel for refractory or recurrent epithelial ovarian cancer patients in Thailand. Asian Pac J Cancer Prev, 14, 2421-7. https://doi.org/10.7314/APJCP.2013.14.4.2421
  23. Poole CJ, Perren T, Gawande S, et al (2006). Optimized sequence of drug administration and schedule leads to improved dose delivery for gemcitabine and paclitaxel in combination: a phase I trial in patients with recurrent ovarian cancer. Int J Gynecol Cancer, 16, 507-14. https://doi.org/10.1111/j.1525-1438.2006.00466.x
  24. Rose PG (2005). Gemcitabine reverses platinum resistance in platinum-resistant ovarian and peritoneal carcinoma. Int J Gynecol Cancer, 15, 18-22. https://doi.org/10.1111/j.1525-1438.2005.15357.x
  25. Rose PG, Mossbruger K, Fusco N, et al (2003). Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma. Gynecol Oncol, 88, 17-21. https://doi.org/10.1006/gyno.2002.6850
  26. Sehouli J, Stengel D, Oskay G, et al (2002). NOGGO study group. A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy. Ann Oncol, 13, 1749-55. https://doi.org/10.1093/annonc/mdf294
  27. Shapiro JD, Millward MJ, Rischin D, et al (1996). Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel. Gynecol Oncol, 63, 89-93. https://doi.org/10.1006/gyno.1996.0284
  28. Su A, Zhang J, Pan ZH, Zhou QM, Lv X (2013). Salvage therapy of gemcitabine plus endostar significantly improves progression-free survival (PFS) with platinum-resistant recurrent epithelial ovarian cancer. Asian Pac J Cancer Prev, 14, 1841-6. https://doi.org/10.7314/APJCP.2013.14.3.1841
  29. Suprasert P, Cheewakriangkrai C, Manopunya M (2012). Outcome of single agent generic gemcitabine in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma. Asian Pac J Cancer Prev, 13, 517-20. https://doi.org/10.7314/APJCP.2012.13.2.517
  30. Suprasert P, Manopunya M, Cheewakriangkrai C (2014). Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience. Asian Pac J Cancer Prev, 15, 1145-8. https://doi.org/10.7314/APJCP.2014.15.3.1145
  31. Watanabe Y, Koike E, Nakai H, Etoh T, Hoshiai H (2008). Phase II study of single-agent gemcitabine in heavily pretreated Japanese patients with recurrent ovarian cancer. Int J Clin Oncol, 13, 345-8. https://doi.org/10.1007/s10147-008-0765-3
  32. Yoshino K, Hiramatsu K, Enomoto T, et al (2012). Salvage chemotherapy using gemcitabine for taxane/platinum-resistant recurrent ovarian cancer: a single institutional experience. Anticancer Res, 32, 4029-33.
  33. Yuan SF, Zhang LP, Zhu LJ, et al (2013). Phase II clinical study on the GEMOX regimen as second- line therapy for advanced ovarian cancer. Asian Pac J Cancer Prev, 14, 3949-53. https://doi.org/10.7314/APJCP.2013.14.6.3949

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