Seminars in Oncology
Volume 33 , Pages 17-25 , April 2006

Optimizing Gemcitabine Regimens in Ovarian Cancer

  • Sergio Pecorelli

      Affiliations

    • Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Italy
    • Prof Pecorelli served as member of the Eli Lilly International Scientific Advisory Board in September 2005.
    • Corresponding Author InformationAddress reprint requests to Prof Sergio Pecorelli, 2nd Division of Obstetrics and Gynecology, University of Brescia, Pz.le Spedali Civili no. 1, I-25123 Brescia, Italy.
  • ,
  • Brunella Pasinetti

      Affiliations

    • Gynecologic Oncology, University of Brescia, Italy.
  • ,
  • Giancarlo Tisi

      Affiliations

    • Gynecologic Oncology, University of Brescia, Italy.
  • ,
  • Franco Odicino

      Affiliations

    • Gynecologic Oncology, University of Brescia, Italy.

References 

  1. Jemal A , Siegel R , Ward E , et al.   Cancer statistics, 2006 . CA Cancer J Clin . 2006;56:106–130
  2. Society for Gynecologic Oncologists: New directions in ovarian cancer research. Report of the Strategic Planning Conference, December 8–9, 1997. Available at: http://www3.cancer.gov/ovarian.pdf (accessed Feb 17, 2006)
  3. Ozols RF , Young RC . Chemotherapy of ovarian cancer . Semin Oncol . 1991;18:222–232
  4. Advanced Ovarian Cancer Trialists Group . Chemotherapy in advanced ovarian cancer – An overview of randomised clinical trials . BMJ . 1991;303:884–893
  5. Young RC , Walton LA , Ellenberg SS , et al.   Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials . N Engl J Med . 1990;322:1021–1027
  6. Trimbos JB , Vergote I , Bolis G , et al.   Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma (European Organisation for Research and Treatment of Cancer - Adjuvant Chemotherapy in Ovarian Neoplasm Trial) . J Natl Cancer Inst . 2003;95:113–125
  7. Trimbos JB , Parmar M , Vergote I , et al.   International Collaborative Ovarian Neoplasm trial 1 and Adjuvant Chemotherapy in Ovarian Neoplasm trial (Two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma) . J Natl Cancer Inst . 2003;95:105–112
  8. Bell J , Brady M , Lage J , et al.   A randomized phase III trial of three versus six cycles of carboplatin paclitaxel as adjuvant treatment in early stage ovarian epithelial carcinoma (A Gynecologic Oncology Group study) . Gynecol Oncol . 2003;85:156; (abstr)
  9. McGuire WP , Hoskins WJ , Brady MF , et al.   Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer . N Engl J Med . 1996;334:1–6
  10. Piccart MJ , Bertelsen K , James K , et al.   Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer (Three-year results) . J Natl Cancer Inst . 2000;92:699–708
  11. Landis SH , Murray T , Bolden S , et al.   Cancer statistics, 1999 . CA Cancer J Clin . 1999;49:8–31
  12. Markman M , Hall J , Spitz D , et al.   Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer . J Clin Oncol . 2002;20:2365–2369
  13. Markman M , Hoskins W . Responses to salvage chemotherapy in ovarian cancer (A critical need for precise definitions of the treated population) . J Clin Oncol . 1992;10:513–514
  14. Gordon AN , Fleagle JT , Guthrie D , et al.   Recurrent epithelial ovarian carcinoma (A randomized phase III study of pegylated liposomal doxorubicin versus topotecan) . J Clin Oncol . 2001;19:3312–3322
  15. du Bois A , Luck HJ , Meier W , et al.   A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer . J Natl Cancer Inst . 2003;95:1320–1329
  16. Neijt JP , Engelholm SA , Tuxen MK . Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer . J Clin Oncol . 2000;18:3084–3092
  17. Parmar MK , Ledermann JA , Colombo N , et al.   Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer (The ICON4/AGO-OVAR-2.2 trial) . Lancet . 2003;361:2099–2106
  18. Markman M . Single-agent carboplatin is the treatment of choice in recurrent, potentially platinum-sensitive epithelial ovarian cancer . In: ASCO Educational Book . Baltimore, MD: Lippincott Williams & Wilkins; 2002;p. 521–523
  19. Bookman MA , Greer BE , Ozols RF . Optimal therapy of advanced ovarian cancer (Carboplatin and paclitaxel versus cisplatin and paclitaxel (GOG158) and an update on GOG0182-ICON5) . Int J Gynecol Cancer . 2003;13(suppl 2):149–155
  20. Huang C , Chubb S , Hertel LW , et al.   Action of 2′2′ difluorodeoxycytidine on DNA synthesis . Cancer Res . 1991;51:6110–6117
  21. Lund B , Krisjansen PE , Hansen HH . Clinical and preclinical activity of 2′, 2′ difluorodeoxycytidine (gemcitabine) . Cancer Treat Rev . 1993;19:45–55
  22. Cartee L , Kucera GL . Gemcitabine induces programmed cell death and activates protein kinase C in BG-1 human ovarian cancer cells . Cancer Chemother Pharmacol . 1998;41:403–412
  23. Orlando M , Mandachain M . Gemcitabine in ovarian cancer . Semin Oncol . 2001;28(suppl 10):62–69
  24. Markman M . Second-line treatment of ovarian cancer with single-agent gemcitabine . Semin Oncol . 2002;29(suppl 1):9–10
  25. Ozols RF . The current role of gemcitabine in ovarian cancer . Semin Oncol . 2001;28(suppl 7):18–24
  26. Gadducci A , Conte P , Cianci C , et al.   Treatment options in patients with recurrent ovarian cancer . Anticancer Res . 2001;21:3557–3564
  27. Maenpaa JU . Docetaxel (Promising and novel combinations in ovarian cancer) . Br J Cancer . 2003;89(suppl 3):29–34
  28. Lorusso D , Ferrandina G , Lo Voi R , et al.   Role of pegylated liposomal doxorubicin (PLD) in epithelial ovarian cancer . J Chemother . 2004;16(suppl 4):98–103
  29. Colombo N , Parma G , Bocciolone L , et al.   Medical therapy of advanced malignant epithelial tumours of the ovary . Forum (Genova) . 2000;10:323–332
  30. Ozols RF . The role of gemcitabine in the treatment of ovarian cancer . Semin Oncol . 2000;27(suppl 2):40–47
  31. Manetta A , Tewari K , Podczaski ES . Hexamethylmelamine as a single second-line agent in ovarian cancer (Follow-up report and review of the literature) . Gynecol Oncol . 1997;66:20–26
  32. Schilder RJ , Scher RM , Young RC . Gynecologic malignancies . Cancer Chemother Biol Response Modif . 1993;14:530–556
  33. Ozols RF . Oral etoposide for the treatment of recurrent ovarian cancer . Drugs . 1999;58(suppl 3):43–49
  34. Muggia FM . Recent updates in the clinical use of platinum compounds for the treatment of gynecologic cancers . Semin Oncol . 2004;31(suppl 14):17–24
  35. Fung MF , Johnston ME , Eisenhauer EA , et al.   Chemotherapy for recurrent epithelial ovarian cancer previously treated with platinum - A systematic review of the evidence from randomized trials . Eur J Gynaecol Oncol . 2002;23:104–110
  36. Morris R , Munkarah A . Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer . Oncologist . 2002;7(suppl 5):29–35
  37. Harries M , Gore M . Part II (Chemotherapy for epithelial ovarian cancer-treatment of recurrent disease) . Lancet Oncol . 2002;3:537–545
  38. ten Bokkel Huinink W , Gore M , Carmichael J , et al.   Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer . J Clin Oncol . 1997;15:2183–2193
  39. Piccart MJ , Green JA , Lacave AJ , et al.   Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer (A randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group) . J Clin Oncol . 2000;18:1193–1202
  40. Andersson H , Bowman K , Ridderheim M , et al.   Updated analysis of a randomized study of single agent paclitaxel given weekly versus every three weeks to patients with ovarian cancer treated with prior platinum therapy . Proc Am Soc Clin Oncol . 1999;18:367a; (abstr)
  41. Parmar MK , Ledermann JA , Colombo N , et al.   Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer (The ICON4/AGO-OVAR-2.2 trial) . Lancet . 2003;361:2099–2106
  42. Rose PG . Gemcitabine reverses platinum resistance in platinum-resistant ovarian and peritoneal carcinoma . Int J Gynecol Cancer . 2005;15(suppl 1):18–22
  43. Bookman MA . Gemcitabine monotherapy in recurrent ovarian cancer (From the bench to the clinic) . Int J Gynecol Cancer . 2005;15(suppl 1):12–17
  44. Gordon AN , Granai CO , Rose PG , et al.   Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer . J Clin Oncol . 2000;18:3093–3100
  45. Caldas C , McGuire WP . Paclitaxel (Taxol) therapy in ovarian carcinoma . Semin Oncol . 1993;20(suppl 3):50–55
  46. Harries M , Kaye SB . Recent advances in the treatment of epithelial ovarian cancer . Expert Opin Invest Drugs . 2001;10:1715–1724
  47. Herzog TJ . Clinical experience with topotecan in relapsed ovarian cancer . Gynecol Oncol . 2003;90:3–7
  48. Lund B , Hansen OP , Neijt JP , et al.   Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients . Anticancer Drugs . 1995;6(suppl 6):61–62
  49. Friedlander M , Millward MJ , Bell D , et al.   A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer . Ann Oncol . 1998;9:1343–1345
  50. von Minckwitz G , Bauknecht T , Visseren-Grul CM , et al.   Phase II study of gemcitabine in ovarian cancer . Ann Oncol . 1999;10:853–855
  51. Markman M , Kennedy A , Webster K , et al.   Phase 2 trial of single-agent gemcitabine (GEM) in platinum (PLAT)/paclitaxel (PAC) refractory ovarian cancer (ROC) . Proc Am Soc Clin Oncol . 2001;20:204a; (abstr 813)
  52. Markman M , Webster K , Zanotti K , et al.   Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer . Gynecol Oncol . 2003;90:593–596
  53. D’Agostino G , Amant F , Berteloot P , et al.   Phase II study of gemcitabine in recurrent platinum-and paclitaxel-resistant ovarian cancer . Gynecol Oncol . 2003;88:266–269
  54. Bolis G , Scarfone G , Sciatta C , et al.   A phase I/II study of topotecan in combination with carboplatin in recurrent epithelial ovarian cancer . Gynecol Oncol . 2001;83:477–480
  55. Montazeri A , Culine S , Laguerre B , et al.   Individual adaptive dosing of topotecan in ovarian cancer . Clin Cancer Res . 2002;8:394–399
  56. Tournigand C , Louvet C , Molitor JL , et al.   Long-term survival with consolidation intraperitoneal chemotherapy for patients with advanced ovarian cancer with pathological complete remission . Gynecol Oncol . 2003;91:341–345
  57. Guastalla JP , Pujade-Lauraine E , Weber B , et al.   Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens) phase II study . Ann Oncol . 1998;9:37–43
  58. Orlando M , Nadal J , Chacón R . Gemcitabine (G) and carboplatin (C) in patients (Pts) with relapsed ovarian cancer (ROC) (A phase I-II study) . Proc Am Soc Clin Oncol . 2000;19:1594; (abstr)
  59. Du Bois A , Luck HJ , Pfisterer J , et al.   Second-line carboplatin and gemcitabine in platinum sensitive ovarian cancer-a dose-finding study by the Arbeitgemeinschaft Gynakologische Onkologie (AGO) Ovarian Cancer Study Group . Ann Oncol . 2001;12:1115–1120
  60. Soh LT , Ho TH . Gemcitabine plus carboplatin in patients with paclitaxel and platinum-resistant epithelial ovarian cancer . Int J Gynecol Cancer . 1999;9(suppl 1):15; (abstr)
  61. Kose MF , Sufliarsky J , Beslija S , et al.   A phase II study of gemcitabine plus carboplatin in platinum-sensitive, recurrent ovarian carcinoma . Gynecol Oncol . 2005;96:374–380
  62. Papadimitriou CA , Fountzilas G , Aravantinos G , et al.   Second-line chemotherapy with gemcitabine and carboplatin in paclitaxel-pretreated, platinum-sensitive ovarian cancer patients. A Hellenic Cooperative Oncology Group Study . Gynecol Oncol . 2004;92:152–159
  63. Safra T , Jeffers S , Groshen S , et al.   Gemcitabine + amifostine + cisplatin (GAP) in pretreated epithelial ovarian cancer . Proc Am Soc Clin Oncol . 1999;18:1481; (abstr)
  64. Blanco-Aparicio C , Pequeno B , Moneo V , et al.   Inhibition of phosphatidylinositol-3-kinase synergizes with gemcitabine in low-passage tumor cell lines correlating with Bax translocation to the mitochondria . Anticancer Drugs . 2005;16:977–987
  65. Nagourney RA , Brewer CA , Radecki S , et al.   Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients . Gynecol Oncol . 2003;88:35–39
  66. Rose PG , Mossbruger K , Fusco N , et al.   Gemcitabine reverses cisplatin resistance (Demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma) . Gynecol Oncol . 2003;88:17–21
  67. Garcia AA , O’Meara A , Bahador A , et al.   Phase II study of gemcitabine and weekly paclitaxel in recurrent platinum-resistant ovarian cancer . Gynecol Oncol . 2004;93:493–498
  68. Trudeau MG , Fox SB , Samson B , et al.   Docetaxel and gemcitabine is an effective regimen in platinum-resistant ovarian cancer (A pilot study from the CICM) . Proc Am Soc Clin Oncol . 2003;22:484; (abstr 1951)
  69. Greggi S , Salerno MG , D’Agostino G , et al.   Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer . Oncology . 2001;60:19–23
  70. Sehouli J , Stengel D , Oskay G , et al.   A new therapeutical approach (Topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy with paclitaxel and platinum) . J Obstet Gynaecol Res . 2003;29:123–131
  71. D’Agostino G , Ferrandina G , Ludovisi M , et al.   Phase II study of liposomal doxorubicin and gemcitabine in the salvage treatment of ovarian cancer . Br J Cancer . 2003;89:1180–1184
  72. Tobias D , Runowicz C , Mandeli J , et al.   A phase I trial of gemcitabine and Doxil for recurrent epithelial ovarian cancer . Proc Am Soc Clin Oncol . 2000;19:1551; (abstr)
  73. Spanu PG , Ferrero AM , Fuso L , et al.   Gemcitabine and vinorelbine in relapsed epithelial ovarian cancer (A phase II study) . Proc Am Soc Clin Oncol . 2001;20:213a; (abstr 848)
  74. Geertsen P , Hansen M , Stroyer I , et al.   Combination chemotherapy with platinum, paclitaxel, and gemcitabine in patients with relapsed ovarian carcinoma . Proc Am Soc Clin Oncol . 1999;18:1395; (abstr)
  75. Pfisterer J , Vergote I , Du Bois A , et al.   Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer . Int J Gynecol Cancer . 2005;15(suppl 1):36–41
  76. Ozols RF . Future directions in the treatment of ovarian cancer . Semin Oncol . 2002;29(suppl 1):32–42
  77. Nogué M , Cirera M , Arcusa I , et al.   Gemcitabine combined with cisplatin first line (A phase II study in patients with advanced epithelial ovarian cancer) . Proc Am Soc Clin Oncol . 1998;17:357a; (abstr 1377)
  78. Krakowski I , Petit T , Kayitalire L , et al.   Gemcitabine in combination with cisplatin in advanced ovarian cancer (A phase II study) . Proc Am Soc Clin Oncol . 1998;17:356a; (abstr 1373)
  79. Belpomme D , Krakowski I , Beauduin M , et al.   Gemcitabine combined with cisplatin as first-line treatment in patients with epithelial ovarian cancer (A phase II study) . Gynecol Oncol . 2003;91:32–38
  80. Bauchnecht T , Grieshaberch C , Breitbach G-P , et al.   Gemcitabine in combination with cisplatin in previously untreated patients >60 years with FIGO stage IIC or IV epithelial ovarian cancer: A phase II study: preliminary results . Proc Am Soc Clin Oncol . 2003;17:356a; (abstr 1376)
  81. Harries M , Moss C , Perren T , et al.   A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer . Br J Cancer . 2004;91:627–632
  82. du Bois A , Belau A , Wagner U , et al.  Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR)   A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8) . Gynecol Oncol . 2005;96:444–451
  83. Hansen SW , Anderson H , Boman K , et al.   Gemcitabine, carboplatin, and paclitaxel (GCP) as first-line treatment of ovarian cancer FIGO stages IIB-IV . Proc Am Soc Clin Oncol . 1999;18:1379; (abstr)
  84. Gupta S , Arora R , Subhasini J , et al.   Gemcitabine, paclitaxel, and cisplatin in chemotherapy naïve advanced ovarian cancer (Results of a multi-center phase II study) . Proc Am Soc Clin Oncol . 2002;21:215a; (abstr 857)
  85. Plunkett W , Huang P , Gandhi V . Preclinical characteristics of gemcitabine . Anticancer Drugs . 1995;6(suppl 6):7–13

PII: S0093-7754(06)00121-7

doi: 10.1053/j.seminoncol.2006.03.014

Seminars in Oncology
Volume 33 , Pages 17-25 , April 2006