Aktuelle und zukünftige Entwicklungen in der Diagnostik und Therapie des Ovarialkarzinoms

Zusammenfassung

Das Ovarialkarzinom ist das fünfthäufigste Karzinom der Frau. Die Prognose des frühen epithelialen Ovarialkarzinoms ist günstig mit einer 5-Jahres-Überlebensrate von über 80 %. Bei den fortgeschrittenen Stadien hat die 5-Jahres-Überlebensrate für das Stadium FIGO IIIC laut FIGO Annual Report seit den 60er-Jahren von weit unter 10 auf 28,7 % in den Jahren 1993 - 1995 zugenommen. Seit Mitte der 90er-Jahre ist jedoch nur eine geringfügige Verbesserung der Überlebensrate auf 32,5 % (1999 - 2001) zu verzeichnen [[1]]. Im Folgenden werden deshalb die aktuellen und zukünftigen Entwicklungen in Diagnostik und Therapie des Ovarialkarzinoms dargestellt, von denen eine Verbesserung der Prognose erhofft wird. Bezüglich des aktuellen Therapiestandards beim Ovarialkarzinom wird auf die 2007 von der Kommission Ovar der AGO herausgegebene interdisziplinäre S2k-Leitlinie verwiesen [[2]].

Abstract

Ovarian cancer is the fifth most common cancer diagnosis in women. The prognosis for early epithelial ovarian carcinoma is favorable with a five-year survival rate of more than 80 %. According to the FIGO annual report, even for advanced stages the 5-year survival rate for FIGO Stage IIIC improved in the years 1993 - 1995 from far below 10 to 28.7 %. However, since the mid nineties only a small improvement in survival (five-year survival rate 32.5 %) was noted. Present and future developments in the diagnosis and treatment of ovarian cancer expected to improve patient outcomes are summarized below. Reference is made to the current standards for ovarian cancer treatment outlined in the interdisciplinary S2 Consensus Guidelines published by the Kommission Ovar of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) in 2007.

Schlüsselwörter

epitheliales Ovarialkarzinom - neue Entwicklungen

Key words

epithelial ovarian cancer - new developments

Literatur

• 1 Heintz A P, Odicino F, Maisonnueve P, Beller U, Benedet J L, Creasman W T. et al . Carcinoma of the ovary.  Int J Gynecol Obstet. 2006;  95 S161-S192
• 2 Interdisziplinäre S2 k Leitlinie für die Diagnostik und Therapie maligner Ovarialtumoren. Herausgegeben von der Kommission Ovar der Arbeitsgemeinschaft Gynäkologische Onkologie in der Deutschen Krebsgesellschaft e.V. sowie in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe. München, Wien, New York; Zuckschwert Verlag 2007
• 3 Smith L H, Morris C R, Yasmenn S, Parikh-Patel A, Cress R D, Romano P S. Ovarian Cancer: Can we make diagnosis earlier?.  Cancer. 2005;  104 1398-1404
• 4 Goff A B, Mandel L S, Drescher C W, Urban N, Gough S, Schurmna K M, Patras J, Mahony B S, Andrsen M R. Development of an ovarian cancer symptom index.  Cancer. 2006;  109 221-227
• 5 Ovarian Cancer Symptoms Consensus Statement. http://www.ovariancancercoalition.org/pdf_worddoc/pressrelease/SGO%20symptom_consensusl.pdf . 
• 6 Skates S J, Menon U, MacDonald N, Rosenthal A N, Oram D H, Knapp R C, Jacobs I J. Calculation of the risk of ovarian cancer from serial CA‐125 values for preclinical detection in postmenopausal women.  J Clin Oncol. 2003;  21 206s-210s
• 7 Van Nagell J R, De Priest P D, Ueland F R, DeSimone C P, Cooper A L, Mc Donald J M, Pavlik E J, Kryscio R J. Ovarian cancer screening with annual transvaginal sonography: findings of 25,000 women screened.  Cancer. 2007;  109 1887-1896
• 8 Buys S S, Partridge E, Greene M JH, Prorok P C, Reding D, Riley T L, Harge P, Fagerstrom R M, Ragard L R, Izmirlan G, Fouad M, Johnson C C, Gohagan J K. PLCO Project Team . Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial.  Am J Obstet Gynecol. 2005;  193 1630-1639
• 9 http://www.ukctocs.org.uk/
• 10 Risch H A, McLaughlin J R, Cole D E, Rosen B, Bradley L, Kwan E, Jack E, Vesprini D J, Kuperstein G, Abrahamson J L, Fan I, Wong B, Narod S A. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer.  Am J Hum Genet. 2001;  68 700-710
• 11 Olivier R I, Lubsen-Brandsma M A, Verhoef S, van Beurden M. CA125 and transvaginal ultrasound monitoring in high risk women cannot prevent the diagnosis of advanced ovarian cancer.  Gynecol Oncol. 2006;  100 20-26
• 12 Kauff N D, Barakat R R. Risk reducing salpingo-oophorectomy in patients with germline mutations in BRCA1 or BRCA2.  J Clin Oncol. 2007;  25 2921-2927
• 13 Zhang H, Kong B, Qu X, Jia L, Deng B, Yang Q. Biomarker discovery for ovarian cancer using SELDI‐TOF‐MS.  Gynecol Oncol. 2006;  102 61-66
• 14 Lu K H, Patterson A P, Wang L, Marquez R T, Atkinson E N, Baggerly K A, Ramoth L R, Rosen D G, Liu J, Hellstrom I, Smith D, Hartmann L, Fishman D, Berchuck A, Schmandt R, Whitaker R, Gershenson D M, Mills G B, Bast R C. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis.  Clin Canc Res. 2004;  10 3291-3300
• 15 Baggerly K A, Morris J S, Edmonson S R, Coombes K R. Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer.  J Natl Cancer Inst. 2005;  97 307-309
• 16 Stäbler A, Diebold J. Molekularpathologie der epithelialen Ovarialneoplasien: Von der Phänotyp-Genotyp Korrelation zu neuen Ansatzpunkten in Diagnostik und Therapie.  Pathologe. 2007;  28 180-186
• 17 Sato N, Tsunoda H, Nihisda M, Morishita Y, Takimoto Y, Kubo T, Noguchi M. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary.  Cancer Res. 2000;  60 7052-7056
• 18 Meinhold-Heerlein I, Bauerschlag D, Hilpert F, Dimitrov P, Sapinoso L M, Orlowska-Volk M, Bauknecht T, Park T W, Jonat W, Jacobsen A, Sehouli J, Luttges J, Krajewski M, Krajewski S, Reed J C, Arnold N, Hampton G M. Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential.  Oncogene. 2005;  24 1053-1065
• 19 Shih I, Kurman R J. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis.  Am J Pathol. 2004;  164 1511-1518
• 20 Helleman J, Jansen M P, Span P N, van Staveren I L, Massuger L F, Meijer-van Gelder M E, Sweep F C, Ewing P C, van der Burg M E, Stoter G, Nooter K, Berns E M. Molecular profiling of platinum resistant ovarian cancer.  Int J Cancer. 2006;  118 1963-1971
• 21 Spentzos D, Levine D A, Kolia S, Out H, Boyd J H, Libermann T A, Cannistra S A. Unique gene expression profile based on pathologic response in epithelial ovarian cancer.  J Clin Oncol. 2005;  23 7911-7918
• 22 Dressman H K, Berchuck A, Chan G, Zhai J, Bild A, Sayer R, Cragun J, Clarke J, Whitaker R S, Li L, Gray J, Marks J, Ginsburg G S, Potti A, West M, Nevins J R, Lancaster J M. An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer.  J Clin Oncol. 2007;  25 517-525
• 23 Trimbos J B, Vergote I, Bolis G, Vermorken J B, Mangioni C, Madronal C. 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
• 24 Tropé C, Kaern J. Adjuvant chemotherapy for early stage ovarian cancer: review of the literature.  J Clin Oncol. 2007;  25 2909-2920
• 25 Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart A M, Torri V, Williams C, Lissoni A, Bonazzi C. International Collaborative Ovarian Neoplasm collaborators (ICON) . International Collaborative Ovarian Neoplasm Trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer.  J Natl Cancer Inst. 2003;  95 125-132
• 26 Swart A C. ICON collaborators . Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON 1).  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # 5509
• 27 Bell J, Brady M F, Young R C, Lage J, Walker J L, Look K Y, Rose G S, Spirtos N M. Gynecologic Oncology Group . Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study.  Gynecol Oncol. 2006;  102 432-439
• 28 Chi D S, Eisenhauer E L, Lang J H, Haddad L, Abu-Rustum N R, Sonoda Y, Levine D A, Hensley M, Barakat R R. What is the optimal goal of primary cytoreductive surgery for bulky stage III c epithelial ovarian carcinoma (EOC).  Gyn Oncol. 2006;  103 559-564
• 29 Eisenhauer E L, Abu-Rustum N R, Sonoda Y, Levine D A, Poynor E A, Aghajanian C, Jarnagin W R, DeMatteo R P, D'Angelica M I, Barakat R R, Chi D S. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC - IV epithelial ovarian cancer.  Gyn Oncol. 2006;  103 1083-1090
• 30 Aletti G D, Dowdy S C, Podratz K C, Cliby W A. Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer.  Gyn Oncol. 2006;  100 283-287
• 31 Panici P B, Maggioni A, Hacker N, Landoni F, Ackermann S, Campagnutta E, Tamussino K, Winter R, Pellegrino A, Greggi S, Angioli R, Manci N, Scambia G, Dell'Anna T, Fossati R, Floriani I, Rossi R S, Grassi R, Favalli G, Raspagliesi F, Giannarelli D, Martella L, Mangioni C. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial.  J Natl Cancer Inst. 2005;  97 560-566
• 32 Bristow R E, Eisenhauer E L, Santillan A, Chi D S. Delaying the primary surgical effort for advanced ovarian cancer: A systematic review of neoadjuvant chemotherapy and interval cytoreduction.  Gynecol Oncol. 2007;  104 480-490
• 33 http://www.eortc.be/protoc/details.asp?protocol=55971
• 34 Park T W, Jänicke F, Ortmann O, Hilfrich J, Breitbach G P, Höss C, Möbus V, Thomssen C, Diedrich K, Maire-Palmedo J, Kuhn W. Eine randomisierte, multizentrische Phase II Studie zur neoadjuvanten Chemotherapie beim fortgeschrittenen Ovarialkarzinom (PRIMOVAR‐1).  Geburtsh Frauenheilk. 2006;  S1 67
• 35 Bristow R E, Chi D S. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: A meta-analysis.  Gynecol Oncol. 2006;  103 1070-1076
• 36 Greer B E, Bundy B N, Ozols R F. Implications of second-look laparotomy in the context of optimally resected Stage III ovarian cancer: A non randomized comparison using an explanatory analysis: A GOG Study.  Gynecol Oncol. 2005;  99 71-79
• 37 Salani R, Santillan A, Zahurak M L, Giuntoli 2nd R L. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome.  Cancer. 2007;  109 685-691
• 38 Harter P, Bois A, Hahmann M, Hasenburg A, Burges A, Loibl S, Gropp M, Huober J, Fink D, Schröder W, Muenstedt K, Schmalfeldt B, Emons G, Pfisterer J, Wollschlaeger K, Meerpohl H G, Breitbach G P, Tanner B, Sehouli J. Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee . Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial.  Ann Surg Oncol. 2006;  13 1702-1710
• 39 Cure H, Battista C, Guastalla J P, Fabbro M, Tubiana N, Bourgeois H, Lioure B, Chiurazzi B, Paraiso D, Pujade-Lauraine E. Phase III randomized trial of high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with advanced ovarian cancer (AOC): 5-year follow-up of a GINECO/FNCLCC/SFGM‐TC study.  J Clin Oncol. 2004;  22 5006
• 40 Conte P F, Favalli G, Gadducci A, Katsaros D, Benedetti Panici P L, Carpi A, Scambia G, Ballardini M, Nanni O, Pecorelli S. et al . Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT).  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # 5505
• 41 Vasey P A, Jayson G C, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye S B. 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
• 42 Sehouli J, Stengel D, Mustea A, Camara O, Keil E, Elling D, Ledwon P, Christiansen B, Klare P, Gebauer G, Schwarz M, Lichtenegger W. Ovarian Cancer Study Group of the Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie . Weekly paclitaxel and carboplatin (PC‐W) for patients with primary advanced ovarian cancer: results of a multicenter phase-II study of the NOGGO.  Cancer Chemother Pharmacol. 2008;  61 243-250
• 43 Abushahin F, Singh D K, Lurain J R, Grendys E C, Rademaker A W, Schink J C. Weekly topotecan for recurrent platinum resistant ovarian cancer.  Gynecol Oncol. 2008;  108 53-57
• 44 http://www.noggo.de
• 45 Armstrong D K, Bundy B N, Baergen R, Lele S B, Copeland L J, Walker J, Burger R. Randomized phase III study of intravenous (IV) paclitaxel and cisplatin versus IV paclitaxel, intraperitoneal (IP) cisplatin and IP paclitaxel in optimal stage III epithelial ovarian cancer (OC): a Gynecologic Oncology Group trial (GOG 172).  Proc Am Soc Clin Oncol. 2002;  21 203a
• 46 Krasner C N, Seiden M V, Fuller A F, Supko J G, Roche M, Kendall D L, Lee J, Berkowitz R, Berlin S, Matulonis U A. Dana Farber/Harvard Cancer Center Gynecologic Oncology Research Group . Results of all-intraperitoneal carboplatin and paclitaxel regimen shows good tolerability and efficacy for advanced ovarian cancer.  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # 5521
• 47 Fujiwara K, Nagao S, Kigawa J, Noma J, Akamatsu N, Miyagi Y, Numa F, Okada M, Aotani E, Terakawa N. Comparative phase II study of intraperitoneal (IP) versus intravenous (IV) carboplatin administration with IV paclitaxel in patients with bulky residual disease after primary debulking surgery for epithelial ovarian or primary peritoneal cancer: A Sankai Gynecology Study Group (SGSG) study.  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # 5584
• 48 Burger R A, Sill M W, Monk B J, Greer B E, Sorosky J I. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study.  J Clin Oncol. 2007;  25 5165-5171
• 49 Cannistra S A, Matulonis U A, Penson R T, Hambleton J, Dupont J, Mackey H, Douglas J, Burger R A, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer.  J Clin Oncol. 2007;  25 5180-5186
• 50 Campos S M, Dizon D S, Cannistra S A, Roche M, Krasner C N, Berlin S T, Horowitz N S, DiSilvestro P, Matulonis U A, Penson R T. Safety of maintenance bevacizumab after first-line chemotherapy for advanced ovarian and müllerian cancers.  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # 5517
• 51 Pfisterer J, du Bois A, Sehouli J, Loibl S, Reinartz S, Reuss A, Canzler U, Belau A, Jackisch C, Kimmig R, Wollschlaeger K, Heilmann V, Hilpert F. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR.  Ann Oncol. 2006;  17 1568-1577
• 52 Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iasonos A, Spriggs D, McGuire W, Reinartz S, Schneider S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K. Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.  Clin Cancer Res. 2006;  12 5503-5510
• 53 Burges A, Wimberger P, Kümper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jäger M, Ströhlein M A, Heiss M M, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study.  Clin Cancer Res. 2007;  13 3899-3905
• 54 Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Spriggs D, Kavangh J, Vermorken J, Brown G L, Kaye S. Canfosfamide (C, TLK286) versus liposomal doxorubicin (D) or topotecan (T) in the third-line treatment of platinum (P) refractory or resistant ovarian cancer (OC): Results of a phase III study.  Suppl to J Clin Oncol. 2007;  25 No 18S Part I # LBA5528

1 (neben der Autorin: A. du Bois, Wiesbaden, A. Burges, München, G. Emons, Göttingen, D. Fink, Zürich, M. Gropp, Düsseldorf, P. Harter, Wiesbaden, A. Hasenburg, Freiburg, S. Hauptmann, Halle, W. Jäger, Dortmund, R. Kimmig, Essen, F. Kommoss, Mannheim, R. Kreienberg, Ulm, W. Kuhn, Bonn, W. Meier, Düsseldorf, K. Münstedt, Gießen, O. Ortmann, Regensburg, J. Pfisterer, Kiel, B. Richter, Radebeul, I. Runnebaum, Jena, W. Schröder, Bremen, J. Sehouli, Berlin, B. Tanner, Berlin, U. Wagner, Marburg)