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Salvage Chemotherapy in Recurrent Platinum-Resistant or Refractory Epithelial Ovarian Cancer with Carboplatin and Distearoylphosphatidylcholine Pegylated Liposomal Doxorubicin (Lipo-Dox®)

  • Khemapech, Nipon ;
  • Oranratanaphan, S. ;
  • Termrungruanglert, W. ;
  • Lertkhachonsuk, R. ;
  • Vasurattana, A.
  • Published : 2013.03.30

Abstract

Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

Keywords

Recurrent ovarian cancer;chemotherapy;salvage therapy;pegylated liposomal doxorubicin

References

  1. A'Hern RP, Gore ME (1995). Impact of doxorubicin on survival in advanced ovarian cancer. J Clin Oncol, 13, 726-32.
  2. Alberts DS, Liu PY, Wilczynski SP et al (2008). Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). Gynecol Oncol, 108, 90-4. https://doi.org/10.1016/j.ygyno.2007.08.075
  3. Bookman MA, Malmstrom H, Bolis G, et al (1998). Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol, 16, 3345-52.
  4. Chou HH, Wang KL, Chen CA, et al (2006). Pegylated liposomal doxorubicin (Lipo-Dox) for platinum-resistant or refractory epithelial ovarian carcinoma: a Taiwanese GynecologicOncology Group study with long-term followup. Gynecol Oncol, 101, 423-8. https://doi.org/10.1016/j.ygyno.2005.10.027
  5. du Bois A, Pfisterer J, Burchardi N, et al (2007).Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynäekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut). Gynecol Oncol, 107, 518-25. https://doi.org/10.1016/j.ygyno.2007.08.008
  6. Fanning J, Bennett TZ, Hilgers RD (1992). Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma. Obstet Gynecol, 80, 954-60.
  7. 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
  8. Ferrandina G, Corrado G, Licameli A, et al (2010). Pegylated liposomal doxorubicin in the management of ovarian cancer. Ther Clin Risk Manag, 6, 463-83.
  9. Ferrero JM, Weber B, Geay JF, et al (2007). Second-line chemotherapy with pegylated Liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial. Ann Oncol, 18, 263-8.
  10. Gabizon A, Meshorer A, Barenholz Y (1986). Comparative longterm study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. J Natl Cancer Inst, 77, 459-69.
  11. Gabizon A, Papahadjopoulos D (1988). Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci USA, 85, 6949-53. https://doi.org/10.1073/pnas.85.18.6949
  12. Gabizon A, Catane R, Uziely B, et al (1994). Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res, 54, 987-92.
  13. Gabizon A, Uziely B, Lotem M, et al (1997). Doxil in patients with pretreated metastatic breast cancer (MBC): a doseschedule finding study with pharmacokinetics. Proc Am Soc Clin Oncol, 16, 516.
  14. Gokhale PC, Radhakrishnan B, Husain SR, et al (1996). An improved method of encapsulation of doxorubicin in liposomes: pharmacological, toxicological and therapeutic evaluation. Br J Cancer, 74, 43-8. https://doi.org/10.1038/bjc.1996.313
  15. Gordon AN, Granai CO, Rose PG, et al (2000). Phase II study of liposomal doxorubicin in platinum-and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol, 18, 3093-100.
  16. Gordon AN, Fleagle JT, Guthrie D, et al (2001). Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol, 19, 3312-22.
  17. Gordon AN, Tonda M, Sun S, Rackoff W (2004). 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, 95, 1-8. https://doi.org/10.1016/j.ygyno.2004.07.011
  18. Grover S, Hill-Kayser CE, Vachani C, et al (2012). Patient reported late effects of gynecological cancer treatment. Gynecol Oncol, 124, 399-403. https://doi.org/10.1016/j.ygyno.2011.11.034
  19. Harashima H, Midori Y, Ohshima S, et al (1993). Kinetic analysis of tissue distribution of doxorubicin incorporated in liposomes in rats (II). Biopharm Drug Dispos, 14, 595-608. https://doi.org/10.1002/bdd.2510140706
  20. Herman EH, Rahman A, Ferrans VJ, Vick JA, Schein PS (1983). Prevention of chronic doxorubicin cardiotoxicity in beagles by liposomal encapsulation. Cancer Res, 43, 5427-32.
  21. Hong RL, Tseng YL (2001). Phase I and pharmacokinetic study of a stable, polyethylene-glycolated liposomal doxorubicin in patients with solid tumors: the relation between pharmacokinetic property and toxicity. Cancer, 91, 1826-33. https://doi.org/10.1002/1097-0142(20010501)91:9<1826::AID-CNCR1203>3.0.CO;2-J
  22. Huang SK, Lee KD, Hong K, Friend DS, Papahadjopoulos D (1992). Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res, 52, 5135-43.
  23. Markman M, Hoskins W (1992). Responses to salvage chemotherapy in ovarian cancer: a critical need for precise definitions of the treated population. J Clin Oncol, 10, 513-4.
  24. Markman M, Kennedy A, Webster K, et al (2000). Phase 2 trial of liposomal doxorubicin (40 mg/m2) in platinum/paclitaxelrefractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Onco, 78, 369-72. https://doi.org/10.1006/gyno.2000.5921
  25. McGuire WP, Hoskins WJ, Brady MF, et al (1996). Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med, 334, 1-6. https://doi.org/10.1056/NEJM199601043340101
  26. Muggia FM, Hainsworth JD, Jeffers S, et al (1997). Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol, 15, 987-93.
  27. Papahadjopoulos D, Allen TM, Gabizon A, et al (1991). Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA, 88, 11460-4. https://doi.org/10.1073/pnas.88.24.11460
  28. Power P, Stuart G, Oza A, et al (2009). Efficacy of pegylated liposomal doxorubicin (PLD) plus carboplatin in ovarian cancer patients who recur within six to twelve months: a phase II study. Gynecol Oncol, 114, 410-4. https://doi.org/10.1016/j.ygyno.2009.04.037
  29. Rahman A, Treat J, Roh JK, et al (1990). A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol, 8, 1093-100.
  30. Rose PG, Fusco N, Fluellen L, Rodriguez M (1998). Second-line therapy with paclitaxel and carboplatin for recurrent disease following first-line therapy with paclitaxel and platinum in ovarian or peritoneal carcinoma. J Clin Oncol, 16, 1494-7.
  31. Safra T, Groshen S, Jeffers S, et al (2001). Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome. Cancer, 91, 90-100. https://doi.org/10.1002/1097-0142(20010101)91:1<90::AID-CNCR12>3.0.CO;2-A
  32. 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
  33. Singal PK, Iliskovic N (1998). Doxorubicin-induced cardiomyopathy. N Engl J Med, 339, 900-5. https://doi.org/10.1056/NEJM199809243391307
  34. Steffensen KD, Waldstom M, Pallisgard N, et al (2013). Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with kras wildtype the palido study, a phase II nonrandomized multicenter study. Int J Gynecol Cancer, 23, 73-80. https://doi.org/10.1097/IGC.0b013e3182775fae
  35. Strother R, Matei D (2009). Pegylated liposomal doxorubicin in ovarian cancer. Ther Clin Risk Manag, 5, 639-50.
  36. Stuart GC, Kitchener H, Bacon M, et al (2011). Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the fourth ovarian cancer consensus conference. Int J Gynecol Cancer, 21, 750-5. https://doi.org/10.1097/IGC.0b013e31821b2568
  37. Williams CJ, Stewart L, Parmar M, Guthrie D (1992). Metaanalysis of the role of platinum compounds in advanced ovarian carcinoma. The advanced ovarian cancer trialists group. Semin Oncol, 19, 120-8.
  38. Yuda T, Maruyama K, Iwatsuru M (1996). Prolongation of liposome circulation time by various derivatives of polyethyleneglycols. Biol Pharm Bull, 19, 1347-51. https://doi.org/10.1248/bpb.19.1347

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