PDF herunterladen
Geburtshilfe Frauenheilkd 2007; 67(8): 823-830
DOI: 10.1055/s-2007-965506
Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Aktuelle Aspekte der Therapie des platinresistenten Ovarialkarzinoms

Current Aspects in the Therapy of Platinum-Resistant Ovarian CancerJ. Sehouli1 , C. Pirvulescu1 , A. Mustea1 , D. Koensgen1 , W. Lichtenegger1 , G. Oskay-Özcelik1
  • 1Department of Gynecology and Obstetrics, Charité, Campus Virchow-Klinikum, University Medicine of Berlin
Weitere Informationen

Publikationsverlauf

eingereicht 13.2.2007 revidiert 29.5.2007

akzeptiert 12.6.2007

Publikationsdatum:
22. August 2007 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Die Operation mit dem Ziel der maximalen Tumorreduktion gefolgt von einer systemischen Chemotherapie mit Paclitaxel und Carboplatin sind die entscheidenden Therapieschritte im Management von fortgeschrittenem Ovarialkarzinom. Trotz der hohen Ansprechraten auf die Chemotherapie rezidiviert der Großteil der Patientinnen. Für die Therapiewahl in der Rezidivsituation ist besonders das therapiefreie Intervall von Relevanz. Für Patientinnen mit einem platinresistenten Ovarialkarzinom werden zwar verschiedene Therapiemodalitäten wie Chemotherapie und Hormontherapie eingesetzt, die Ansprechraten sind jedoch sehr unbefriedigend. Auf Basis von publizierten Studien und aktueller Leitlinien werden die einzelnen Therapieoptionen diskutiert und auch neue zielgerichtete Therapieansätze vorgestellt.

Abstract

Surgery and chemotherapy form the cornerstone of the primary treatment for advanced ovarian cancer. Currently, the standard of care for primary ovarian cancer is platinum and taxane-based therapy. Despite the favorable response, however, most women with advanced-stage ovarian cancer will relapse. The treatment-free interval after adequate front-line therapy is particularly important for the therapy strategy for relapsed ovarian cancer. Various treatment options are available for patients with platinum resistance who suffer a relapse within 6 months after primary therapy, but there is no clear consensus about how these patients should be managed. Options include palliative surgery, chemotherapy and hormone therapy. The choice of treatment and the form in which any or all of these options should be administered to an individual patient have not yet been standardized and are the subjects of ongoing clinical trials. Based on randomized trials this article gives an overview of the various treatment modalities and discusses new targeted therapies.

Schlüsselwörter

Ovarialkarzinom - Platinresistenz - Chemotherapie

Key words

ovarian cancer - platinum resistance - chemotherapy

Literatur

  • 1 Aghajanian C. Clinical update: novel targets in gynecologic malignancies.  Semin Oncol. 2004;  31 22-31
    PubMedGoogle Scholar
  • 2 Alberts D S, Liu P Y, Hannigan E V, O'Toole R, Williams S D, Young J A, Franklin E W, Clarke-Pearson D L, Malviya V K, DuBeshter B. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.  N Engl J Med. 1996;  335 1950-1955
    CrossrefPubMedGoogle Scholar
  • 3 Ali-Fehmi R, Che M, Khalifeh I, Malone J M, Morris R, Lawrence W D, Munkarah A R. The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma.  Cancer. 2003;  98 1423-1429
    CrossrefPubMedGoogle Scholar
  • 4 Armstrong D K, Bundy B, Wenzel L, Huang H Q, Baergen R, Lele S, Copeland L J, Walker J L, Burger R A. Gynecologic Oncology Group . Intraperitoneal cisplatin and paclitaxel in ovarian cancer.  N Engl J Med. 2006;  354 34-43
    CrossrefPubMedGoogle Scholar
  • 5 Bajetta E, Di Leo A, Biganzoli L, Mariani L, Cappuzzo F, Di Bartolomeo M, Zilembo N, Artale S, Magnani E, Celio L, Buzzoni R, Carnaghi C. Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.  J Clin Oncol. 1996;  14 2546-2551
    PubMedGoogle Scholar
  • 6 Bergman A M, Ruiz van Haperen V W, Veerman G, Kuiper C M, Peters G J. Synergistic interaction between cisplatin and gemcitabine in vitro.  Clin Cancer Res. 1996;  2 521-530
    PubMedGoogle Scholar
  • 7 Boehmer C, Jaeger W. Capecitabine in treatment of platinum-resistant recurrent ovarian cancer.  Anticancer Res. 2002;  22(1A) 439-443
    PubMedGoogle Scholar
  • 8 Bookman M A, Darcy K M, Clarke-Pearson D, Boothby R A, Horowitz I R. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group.  J Clin Oncol. 2003;  21 283-290
    CrossrefPubMedGoogle Scholar
  • 9 Brewer C A, Blessing J A, Nagourney R A, Morgan M, Hanjani P. Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal cancer: a phase II study of the Gynecologic Oncology Group.  Gynecol Oncol. 2006;  103 446-450
    CrossrefPubMedGoogle Scholar
  • 10 Bristow R E, Tomacruz R S, Armstrong D K, Trimble E L, Montz F J. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis.  J Clin Oncol. 2002;  20 1248-1259
    CrossrefPubMedGoogle Scholar
  • 11 Burger R A, Sill M, Monk B J, Greer B, Sorosky J. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): a Gynecologic Oncology Group (GOG) study.  Proc Am Soc Clin Oncol. 2005;  24 a5009
    PubMedGoogle Scholar
  • 12 Cannistra S A, Matulonis U, Penson R, Wenham R, Armstrong D, Burger R A, Mackey H, Douglas J, Hambleton J, McGuire W. Bevacizumab in patients with advanced platinum-resistant ovarian cancer.  Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings;  Vol 24, No 18S (June 20 Supplement), 2006 a5006
    PubMedGoogle Scholar
  • 13 Chambers S K, Chambers J T, Kohorn E I, Lawrence R, Schwartz P E. Evaluation of the role of second-look surgery in ovarian cancer.  Obstet Gynecol. 1988;  72(3 Pt 1) 404-408
    PubMedGoogle Scholar
  • 14 Cree I A. Chemosensitivity testing as an aid to anti-cancer drug and regimen development.  Recent Results Cancer Res. 2003;  161 119-125
    PubMedGoogle Scholar
  • 15 Creemers G J, Bolis G, Gore M, Scarfone G, Lacave A J, Guastalla J P, Despax R, Favalli G, Kreinberg R, Van Belle S, Hudson I, Verweij J, Ten Bokkel Huinink W W. Topotecan. An active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.  J Clin Oncol. 1996;  14 3056-3061
    PubMedGoogle Scholar
  • 16 Denkert C, Kobel M, Pest S, Koch I, Berger S, Schwabe M, Siegert A, Reles A, Klosterhalfen B, Hauptmann S. Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma.  Am J Pathol. 2002;  160 893-903
    PubMedGoogle Scholar
  • 17 Denkert C, Furstenberg A, Daniel P T, Koch I, Kobel M, Weichert W, Siegert A, Hauptmann S. Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti-inflammatory drug NS‐398, but not by COX‐2-specific RNA interference.  Oncogene. 2003;  22 8653-8661
    CrossrefPubMedGoogle Scholar
  • 18 Denkert C, Weichert W, Pest S, Koch I, Licht D, Kobel M, Reles A, Sehouli J, Dietel M, Hauptmann S. Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression.  Cancer Res. 2004;  64 189-195
    CrossrefPubMedGoogle Scholar
  • 19 D'Incalci M, Colombo T, Ubezio P, Nicoletti I, Giavazzi R, Erba E, Ferrarese L, Meco D, Riccardi R, Sessa C, Cavallini E, Jimeno J, Faircloth G T. The combination of yondelis and cisplatin is synergistic against human tumor xenografts.  Eur J Cancer. 2003;  39 1920-1926
    CrossrefPubMedGoogle Scholar
  • 20 du Bois A, Meier W, Luck H J, Emon G, Moebus V, Schroeder W, Costa S, Bauknecht T, Olbricht S, Jackisch C, Richter B, Wagner U. Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised trial of the German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian Cancer.  Ann Oncol. 2002;  13 251-257
    CrossrefPubMedGoogle Scholar
  • 21 Ferrandina G, Lauriola L, Zannoni G F, Fagotti A, Fanfani F, Legge F, Maggiano N, Gessi M, Mancuso S, Ranelletti F O, Scambia G. Increased cyclooxygenase-2 (COX‐2) expression is associated with chemotherapy resistance and outcome in ovarian cancer patients.  Ann Oncol. 2002;  13 1205-1211
    CrossrefPubMedGoogle Scholar
  • 22 Folkman J, Klagsbrun M. Angiogenic factors.  Science. 1987;  235 442-447
    CrossrefPubMedGoogle Scholar
  • 23 Friberg G, Oza A M, Morgan R J, Vokes E E, Gandara D R, Fleming G F. Bevacizumab (B) plus erlotinib (E) for patients (pts) with recurrent ovarian (OC) and fallopian tube (FT) cancer: Preliminary results of a multi-center phase II trial. ASCO 2006: a5018
    Google Scholar
  • 24 Gropp M, Meier W, Hepp H. Treosulfan as an effective second-line therapy in ovarian cancer.  Gynecol Oncol. 1998;  71 94-98
    CrossrefPubMedGoogle Scholar
  • 25 Gordon A N, Tonda M, Sun S, Rackoff W. Doxil Study 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 1-8
    CrossrefPubMedGoogle Scholar
  • 26 Gordon A N, Tonda M, Sun S, Rackoff W. Doxil Study Investigators . Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.  Gynecol Oncol. 2004;  95 1-8
    CrossrefPubMedGoogle Scholar
  • 27 Herzog T J. Recurrent ovarian cancer: how important is it to treat to disease progression?.  Clin Cancer Res. 2004;  10 7439-7449
    CrossrefPubMedGoogle Scholar
  • 28 Hoskins W J, Rubin S C, Dulaney E, Chapman D, Almadrones L, Saigo P, Markman M, Hakes T, Reichman B, Jones W B. Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma.  Gynecol Oncol. 1989;  34 365-371
    CrossrefPubMedGoogle Scholar
  • 29 Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.  N Engl J Med. 2004;  350 2335-2342
    CrossrefPubMedGoogle Scholar
  • 30 Ignoffo R J. Overview of bevacizumab: a new cancer therapeutic strategy targeting vascular endothelial growth factor.  Am J Health Syst Pharm. 2004;  61 S21-26
    PubMedGoogle Scholar
  • 31 Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun M J. Cancer statistics, 2006.  CA Cancer J Clin. 2006;  56 106-130
    Google Scholar
  • 32 Joly F, Joly C, Mangioni C, Nicoletto M, Manikhas G M, Walker J, Mietlowski W, Jones G, Wysowskyj M, Dugan M. A phase 3 study of PSC 833 in combination with paclitaxel and carboplatin (PC-PSC) versus paclitaxel and carboplatin (PC) alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary cancer of the peritoneum (Abstract).  Proc Am Soc Clin Oncol. 2002;  21 806
    PubMedGoogle Scholar
  • 33 Kavanagh J J, Gershenson D M, Choi H, Lewis L, Patel K, Brown G L, Garcia A, Spriggs D R. Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer.  Int J Gynecol Cancer. 2005;  15 593-600
    CrossrefPubMedGoogle Scholar
  • 34 Kaye S B, Piccart M, Francis P, Kavanagh J. Phase II trials of docetaxel (Taxotere) in advanced ovarian cancer - an updated overview.  Eur J Cancer. 1997;  33 2167-2170
    CrossrefPubMedGoogle Scholar
  • 35 Keldsen N, Madsen E L, Havsteen H. The Danish Ovarian Cancer Study Group . Oral treosulfan as secondline treatment in platinum-resistant ovarian cancer: a phase II study.  Gynecol Oncol. 1998;  69 100-102
    CrossrefPubMedGoogle Scholar
  • 36 Kudelka A P, Tresukosol D, Edwards C L, Freedman R S, Levenback C, Chantarawiroj P, Gonzalez de Leon C, Kim E E, Madden T, Wallin B, Hord M, Verschraegen C, Raber M, Kavanagh J J. Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.  J Clin Oncol. 1996;  14 1552-1557
    PubMedGoogle Scholar
  • 37 Kurbacher C, Bruckner H, Cree I, Andreotti P, Janat M. A prospective clinical trial on individualized chemotherapy for recurrent ovarian cancer selected by the ex vivo ATP tumor chemosensitivity assay (meeting abstract). ASCO Annual Meeting. 1999: a1384
    Google Scholar
  • 38 Lage H. ABC-transporters: implications on drug resistance from microorganisms to human cancers.  Int J Antimicrob Agents. 2003;  22 188-199
    PubMedGoogle Scholar
  • 39 Levy T, Inbar M, Menczer J, Grisaru D, Glezerman M, Safra T. Phase II study of weekly topotecan in patients with recurrent or persistent epithelial ovarian cancer.  Gynecol Oncol. 2004;  95 686-690
    CrossrefPubMedGoogle Scholar
  • 40 Lichtenegger W, Sehouli J, Buchmann E, Karajanev C, Weidemann H. Operative results after primary and secondary debulking-operations in advanced ovarian cancer (AOC).  J Obstet Gynaecol Res. 1998;  24 447-451
    PubMedGoogle Scholar
  • 41 Lindner D J, Borden E C. Effects of tamoxifen and interferon-beta or the combination on tumor-induced angiogenesis.  Int J Cancer. 1997;  71 456-461
    CrossrefPubMedGoogle Scholar
  • 42 Loibl S, Du Bois A, Pfisterer J, Huober J, Lueck H J, Sehouli J, Wagner U. AGO Ovarian Cancer Study Group (AGO-OVAR) .Safety, tolerability and activity of gefitinib (ZD1839) in combination with tamoxifen in ovarian cancer patients refractory to platinum-taxane based therapy - a Phase-II study of the Ovarian Cancer Study Group (AGO Ovar 2.6). ASCO. 2006: a5016
    Google Scholar
  • 43 Lund B, Hansen O P, Neijt J P, Theilade K, Hansen M. Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients.  Anticancer Drugs. 1995;  6 61-62
    CrossrefPubMedGoogle Scholar
  • 44 Lynch T J. The evolving story of the epidermal growth factor receptor as a target for non-small-cell lung cancer.  Clin Adv Hematol Oncol. 2004;  2 786-787
    PubMedGoogle Scholar
  • 45 Luftner D, Pollmann D. et al . Perspectives of immunotherapy in metastatic breast cancer.  Anticancer Res. 2005;  25(6C) 4599-4604
    PubMedGoogle Scholar
  • 46 Makhnova E V. Combination chemotherapy with Hemzar (gemcitabine) and cisplatin for relapsing and cisplatin-resistant ovarian cancer.  Vopr Onkol. 2003;  49 60-65
    PubMedGoogle Scholar
  • 47 Markman M, Bookman M A. Second-line treatment of ovarian cancer.  Oncologist. 2000;  5 26-35
    CrossrefPubMedGoogle Scholar
  • 48 Markman M, Bookman M A. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.  J Clin Oncol. 1991;  9 389-393
    PubMedGoogle Scholar
  • 49 Markman M, Hakes T, Reichman B, Lewis Jr J L, Rubin S, Jones W, Almadrones L, Pizzuto F, Hoskins W. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.  J Clin Oncol. 1992;  10 243-248
    PubMedGoogle Scholar
  • 50 Markman M, Iseminger K A, Hatch K D, Creasman W T, Barnes W, Dubeshter B. Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group ancillary report.  Gynecol Oncol. 1996;  62 4-6
    CrossrefPubMedGoogle Scholar
  • 51 Markman M, Blessing J A, Moore D, Ball H, Lentz S S. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial.  Gynecol Oncol. 1998;  69 226-229
    CrossrefPubMedGoogle Scholar
  • 52 Markman M, Bundy B N, Alberts D S, Fowler J M, Clark-Pearson D L, Carson L F, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.  J Clin Oncol. 2001;  19 1001-1007
    PubMedGoogle Scholar
  • 53 Markman M, Webster K, Zanotti K, Kulp B, Peterson G, Belinson J. Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer.  Gynecol Oncol. 2003;  90 593-596
    CrossrefPubMedGoogle Scholar
  • 54 Markman M, Liu P Y, Wilczynski S, Monk B, Copeland L J, Alvarez R D, Jiang C, Alberts D. Southwest Oncology Group . Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial.  J Clin Oncol. 2003;  21 2460-2465
    CrossrefPubMedGoogle Scholar
  • 55 Markman M, Zanotti K, Webster K, Peterson G, Kulp B, Belinson J. Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum.  Gynecol Oncol. 2003;  91 573-576
    CrossrefPubMedGoogle Scholar
  • 56 Markman M, Gordon A N, McGuire W P, Muggia F M. Liposomal anthracycline treatment for ovarian cancer.  Semin Oncol. 2004;  31 91-105
    PubMedGoogle Scholar
  • 57 Markman M, Webster K, Zanotti K, Peterson G, Kulp B, Belinson J. Survival following the documentation of platinum and taxane resistance in ovarian cancer: a single institution experience involving multiple phase 2 clinical trials.  Gynecol Oncol. 2004;  93 699-701
    CrossrefPubMedGoogle Scholar
  • 58 McCreath W A, Chi D S. Surgical cytoreduction in ovarian cancer.  Oncology (Williston Park). 2004;  18 645-653
    PubMedGoogle Scholar
  • 59 McGuire W P, Hoskins W J, Brady M F, Kucera P R, Partridge E E, Look K Y, Clarke-Pearson D L, Davidson M. 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
    CrossrefPubMedGoogle Scholar
  • 60 Meier W, Dubois A, Kuhn W, Pfisterer J, Kimmig R, Olbricht S, Richter B. for the AGO Ovarian Cancer Study Group . Topotecan vs. treosulfan in recurrent ovarian cancer (OC) after initial therapy with platinum and paclitaxel. A prospective randomized phase III study.  Proc Am Soc Clin Oncol. 2003;  22 abstr 1810
    PubMedGoogle Scholar
  • 61 Morris R, Munkarah A. Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer.  The Oncologist. 2002;  7 29-35
    CrossrefPubMedGoogle Scholar
  • 62 Moufarij M A, Phillips D R, Cullinane C. Gemcitabine potentiates cisplatin cytotoxicity and inhibits repair of cisplatin-DNA damage in ovarian cancer cell lines.  Mol Pharmacol. 2003;  63 862-869
    CrossrefPubMedGoogle Scholar
  • 63 Ferrandina G, Lorusso D, Pignata S, Breda E, Savarese A, Nardi M, Scaltriti L, Ludovisi M, Scambia G. The Multicentre Italian Trials in Ovarian cancer (MITO) Group .A randomized phase III study of Gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLD) in progressive/recurrent ovarian cancer (OC). ASCO. 2007: Lba5506
    Google Scholar
  • 64 Nagourney R A, Brewer C A, Radecki S, Kidder W A, Sommers B L, Evans S S, Minor D R, DiSaia P J. Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients.  Gynecol Oncol. 2003;  88 35-39
    CrossrefPubMedGoogle Scholar
  • 65 O'Byrne K J, Bliss P, Graham J D. A phase III study of Doxil/Caelyx versus paclitaxel in platinum-treated taxane-naive relapsed ovarian cancer.  Proc Am Soc Clin Oncol. 2002;  21 203a [Abstract]
    PubMedGoogle Scholar
  • 66 Ozols R F, Bundy B N, Greer B E, Fowler J M, Clarke-Pearson D, Burger R A, Mannel R S, DeGeest K, Hartenbach E M, Baergen R. Gynecologic Oncology Group . 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. 2003;  21 3194-3200
    CrossrefPubMedGoogle Scholar
  • 67 Parmar M K, Ledermann J A, Colombo N, du Bois A, Delaloye J F, Kristensen G B, Wheeler S, Swart A M, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Trope C. ICON and AGO Collaborators . 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
    CrossrefPubMedGoogle Scholar
  • 68 Peters G J, Bergman A M, Ruiz van Haperen V W, Veerman G, Kuiper C M, Braakhuis B J. Interaction between cisplatin and gemcitabine in vitro and in vivo.  Semin Oncol. 1995;  22 72-79
    PubMedGoogle Scholar
  • 69 Pfisterer J, Plante M, Vergote I. Gemcitabine/carboplatin (GC) vs. carboplatin (C) in platinum sensitive recurrent ovarian cancer (OVCA). Results of a Gynecologic Cancer Intergroup randomized phase III trial of the AGO OVAR, the NCIC CTG and the EORTC GCG [abstract].  Proc Am Soc Clin Oncol. 2003;  22 a1951
    PubMedGoogle Scholar
  • 70 Podratz K C, Schray M F, Wieand H S, Edmonson J H, Jefferies J A, Long H J, Malkasian G D, Stanhope C R, Wilson T O. Evaluation of treatment and survival after positive second-look laparotomy.  Gynecol Oncol. 1988;  31 9-24
    CrossrefPubMedGoogle Scholar
  • 71 Rose P G, Blessing J A, Mayer A R, Homesley H D. Prolonged oral etoposide as second line therapy for platinum resistant and platinum sensitive ovarian carcinomas: a Gynecologic Oncology Group study.  J Clin Oncol. 1998;  16 405-410
    CrossrefPubMedGoogle Scholar
  • 72 Rose P G, Blessing J A, Ball H G, Hoffman J, Warshal D, DeGeest K, Moore D H. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study.  Gynecol Oncol. 2003;  88 130-135
    CrossrefPubMedGoogle Scholar
  • 73 Rose P G, Mossbruger K, Fusco N, Smrekar M, Eaton S, Rodriguez M. Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma.  Gynecol Oncol. 2003;  88 17-21
    CrossrefPubMedGoogle Scholar
  • 74 Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, Paro G. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with pre-oral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum.  Acta Oncol. 2002;  41 418-424
    PubMedGoogle Scholar
  • 75 Schink J C, Hams L S, Grosen E A, Bailey H W. Altretamine (Hexalen) An effective salvage chemotherapy after paclitaxel (Taxol) in women with recurrent platinum resistant ovarian cancer [abstract].  Proc Am Soc Clin Oncol. 1995;  14 275
    PubMedGoogle Scholar
  • 76 Sehouli J, Stengel D, Oskay G, Blohmer J, Kaubitzsch S, Lichtenegger W. Ovarian Cancer Study Group of the Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO) . Dose finding study for combination treatment with topotecan and gemcitabine of patients with recurrent ovarian cancer after failure of first-line chemotherapy with paclitaxel and platinum.  Onkologie. 2004;  27 58-64
    CrossrefPubMedGoogle Scholar
  • 77 Sehouli J, Sommer H, Klare P, Stauch M, Zeimet A, Paulenz A, Steck T, Riedel H, Keil E, Stengel D, Kuznik A, Lichtenegger W. on behalf of the NOGGO Study Group Ovarian Cancer . A randomized multicenter phase III trial of topotecan monotherapy versus topotecan + etoposide versus topotecan + gemcitabine for second-line treatment of recurrent ovarian cancer.  J Clin Oncol. 2006;  24 (18S)
    PubMedGoogle Scholar
  • 78 Shapiro J D, Millward M J, Rischin D, Michael M, Walcher V, Francis P A, Toner G C. Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel.  Gynecol Oncol. 1996;  63 89-93
    CrossrefPubMedGoogle Scholar
  • 79 Swisher E M, Mutch D G, Rader J S, Elbendary A, Herzog T J. Topotecan in platinum- and paclitaxel-resistant ovarian cancer.  Gynecol Oncol. 1997;  66 480-486
    CrossrefPubMedGoogle Scholar
  • 80 Tew K D. TLK‐286: a novel glutathione S-transferase-activated prodrug.  pert Opin Investig Drugs. 2005;  14 1047-1054
    PubMedGoogle Scholar
  • 81 Tewari D, Monk B J, Hunter M, Falkner C A, Burger R A. Gemcitabine and cisplatin chemotherapy is an active combination in the treatment of platinum-resistant ovarian and peritoneal carcinoma.  Invest New Drugs. 2004;  22 475-480
    CrossrefPubMedGoogle Scholar
  • 82 Thomas G M, Dembo A J. Integrating radiation therapy into the management of ovarian cancer.  Cancer. 1993;  71 1710-1718
    PubMedGoogle Scholar
  • 83 Thomas H, Rosenberg P. Role of weekly paclitaxel in the treatment of advanced ovarian cancer.  Crit Rev Oncol Hematol. 2002;  44 S43-51
    CrossrefPubMedGoogle Scholar
  • 84 Van der Burgh M E, van der Gaast A, Vergote I, Burger C W, van Doorn H C, de Wit R, Stoter G, Verweij J. What is the role of dose-dense therapy?.  Int J Gynecol Cancer. 2005;  15 233-240
    PubMedGoogle Scholar
  • 85 van Moorsel C J, Pinedo H M, Veerman G, Bergman A M, Kuiper C M, Vermorken J B, van der Vijgh W J, Peters G J. Mechanisms of synergism between cisplatin and gemcitabine in ovarian and non-small-cell lung cancer cell lines.  Br J Cancer. 1999;  80 981-990
    CrossrefPubMedGoogle Scholar
  • 86 Vasey P A, Jayson G C, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye S B. Scottish Gynaecological Cancer Trials Group . Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma.  J Natl Cancer Inst. 2004;  96 1682-1691
    CrossrefPubMedGoogle Scholar
  • 87 Verschraegen C F, Smith H O, Lee F C, Cathcart C, Norenberg J P. TLK‐286.  I Drugs. 2004;  7 771-781
    PubMedGoogle Scholar
  • 88 Yap O W, Kapp D S, Teng N N, Husain A. Intraoperative radiation therapy in recurrent ovarian cancer.  Int J Radiat Oncol Biol Phys. 2005;  63 1114-1121
    CrossrefPubMedGoogle Scholar
  • 89 Williams C J. Tamoxifen for relapse of ovarian cancer.  Cochrane Database Syst Rev. 2001;  (1) CD001034
    PubMedGoogle Scholar
  • 90 Wright J D, Alvarezsecord A, Numnum T M, Rocconi R P, Powell M A, Berchuck A, Alvarez R D, Trinkaus K, Rader J S, Mutch D G. A multi-institutional evaluation of the safety and efficacy of bevacizumab for recurrent, platinum-resistant ovarian cancer. ASCO. 2006: a5019
    Google Scholar
  • 91 Sehouli J, Oskay-Oezcelik G, Stengel D, du Bois A, Markmann S, Loibl S, Wilke J, Nugent A, Belau A, Lichtenegger W. Topotecan weekly versus routine 5-day schedule in patients with platinum-resistant ovarian cancer (TOWER): A randomized, two-stage phase-II study of the North-Eastern German Society of Gynaecological Oncology (NOGGO). ASCO. 2007: a5526
    Google Scholar
  • 92 Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Spriggs D, Kavanagh J, Vermorken J, Brown G L, Kaye D. Single agent, canfosfamide (C, TLK286) vs. pegylated liposomal doxorubicin (D) or topotecan (T) in 3rd-line treatment of platinum (P) refractory or resistant ovarian cancer (OC): Phase 3 study results. ASCO. 2007: Lba5528
    Google Scholar
  • 93 Campos S M, Dizon D S, Cannistra S A, Roche A, Krasner C N, Berlin S T, Horowitz S, DiSilvestro P, Matulonis U A, Penson R T. Safety of maintenance bevacizumab after first-line chemotherapy for advanced ovarian and müllerian cancers. ASCO. 2007: a5517
    Google Scholar
  • 94 Petru E, Schwarz S, Benedicic C, Reuss J, Haas J, Winter R. Goserelin als Palliativtherapie des Ovarial- und Endometriumkarzinoms.  Geburtsh Frauenheilk. 2004;  64 831-834
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 95 Meinhold-Heerlein I, Borges-Engeby K, Grünn U, Bauerschlag D, Maass N, Mundhenke C, Jonat W, Bauknecht T. Untersuchungen zur TRAIL-induzierten Apoptose von Ovarialkarzinomzelllinien mit selektiver Zytostatikaresistenz.  Geburtsh Frauenheilk. 2005;  65 1064-1073
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 96 Fister S, Günthert A, Rivier J, Emons G, Gründker C. Wirkung von Antagonisten des Gonadotropin-Releasing Hormons Typ II (GnRH‐II) auf das Wachstum humaner Ovarialkarzinome in vitro und in vivo.  Geburtsh Frauenheilk. 2006;  67
    PubMedGoogle Scholar
  • 97 Cadron I, Leunen K, Amant F, Van Gorp T, Neven P, Vergote I. The “Leuven” dose-dense paclitaxel/carboplatin regimen in patients with recurrent ovarian cancer.  Gynecol Oncol. 2007;  10
    PubMedGoogle Scholar
  • 98 Belau A, Pfisterer J, Wimberger P, Kurzeder C, Du Bois A, Sehouli J, Loibl S, Burchardi N, Vergote I, Wagner U. Randomized, multicenter, two-dose level, open-label, phase II a study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) to select the better dose level in platinum refractory epithelial ovarian cancer patients. ASCO. 2007: a5556
    Google Scholar

Priv.-Doz. Dr. med. Jalid Sehouli

Universitätsklinikum Charité/Campus Virchow-Klinikum
Klinik für Frauenheilkunde und Geburtshilfe

Augustenburger Platz 1

13353 Berlin

eMail: sehouli@aol.com