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Erschienen in: Der Onkologe 2/2019

14.01.2019 | Ovarialkarzinom | Leitthema

Medikamentöse Therapie des Ovarialkarzinoms in der Primär- und Rezidivsituation

verfasst von: Prof. Dr. med. Frederik Marmé, Philipp Harter, Beyhan Ataseven

Erschienen in: Die Onkologie | Ausgabe 2/2019

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Zusammenfassung

Hintergrund

Das Verständnis der Heterogenität der Tumorbiologie des Ovarialkarzinoms hat in den letzten 10 Jahren rasant zugenommen. Dies hat neben der Einführung der Antiangiogenese als Therapieprinzip auch zur Definition eines zentralen therapeutischen Ziels geführt. Defekte in der homologen Rekombination sind, basierend auf dem Prinzip der synthetischen Letalität, therapeutisch nutzbar und haben zur Einführung der PARP-Inhibitoren als essenziellem Therapiebaustein geführt.

Material und Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche der Datenbank PubMed sowie Abstracts relevanter Kongresse und aktueller nationaler und internationaler Leitlinien.

Ergebnisse

In der letzten Zeit haben sich mit der Antiangiogenese und der Einführung der PARP-Inhibitoren die Behandlungsmöglichkeiten zunehmend diversifiziert. So werden die PARP-Inhibitoren als Erhaltungstherapie den Standard des BRCA-assoziierten Ovarialkarzinoms in der in Zukunft Primärtherapie definieren. Die Kenntnis des BRCA-Status zu Beginn der Primärtherapie ist für eine sinnvolle individuelle Therapieplanung auch im Hinblick auf die Therapiesequenzen unabdingbar. Die streng kalendarisch definierte Einteilung in platinsensitive und -resistente Rezidive wurde verlassen, und die Bedeutung multipler Faktoren für die Entscheidung, ob eine platinhaltige Therapie im Rezidiv sinnvoll erscheint, betont. Die entsprechenden Therapieoptionen werden getrennt nach Primär- und Rezidivtherapie sowie getrennt nach den Therapieprinzipien anhand deren Evidenz diskutiert.

Diskussion

Die Integration effektiver zielgerichteter Therapien hat erstmals zur Wahl zwischen verschiedenen Therapieoptionen geführt. Die klinische Entwicklung über die Antiangiogenese und PARP-Inhibitoren hinaus hat aktuell mit vielen parallelen Phase-III-Studien deutlich Fahrt aufgenommen. Hauptsächlich untersuchen diese die Integration immuntherapeutischer Ansätze in die bestehenden Therapiestrategien.
Literatur
2.
Zurück zum Zitat Collinson F, Qian W, Fossati R, Lissoni A, Williams C, Parmar M et al (2014) Optimal treatment of early-stage ovarian cancer. Ann Oncol 25(6):1165–1171CrossRef Collinson F, Qian W, Fossati R, Lissoni A, Williams C, Parmar M et al (2014) Optimal treatment of early-stage ovarian cancer. Ann Oncol 25(6):1165–1171CrossRef
3.
Zurück zum Zitat Trimbos B, Timmers P, Pecorelli S, Coens C, Ven K, van der Burg M et al (2010) Surgical staging and treatment of early ovarian cancer: long-term analysis from a randomized trial. J Natl Cancer Inst 102(13):982–987CrossRef Trimbos B, Timmers P, Pecorelli S, Coens C, Ven K, van der Burg M et al (2010) Surgical staging and treatment of early ovarian cancer: long-term analysis from a randomized trial. J Natl Cancer Inst 102(13):982–987CrossRef
4.
Zurück zum Zitat Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM et al (2003) International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 95(2):125–132CrossRef Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM et al (2003) International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 95(2):125–132CrossRef
6.
Zurück zum Zitat Chan JK, Tian C, Teoh D, Monk BJ, Herzog T, Kapp DS et al (2010) Survival after recurrence in early-stage high-risk epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 116(3):307–311CrossRef Chan JK, Tian C, Teoh D, Monk BJ, Herzog T, Kapp DS et al (2010) Survival after recurrence in early-stage high-risk epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 116(3):307–311CrossRef
7.
Zurück zum Zitat Chan JK, Tian C, Fleming GF, Monk BJ, Herzog TJ, Kapp DS et al (2010) The potential benefit of 6 vs, 3 cycles of chemotherapy in subsets of women with early-stage high-risk epithelial ovarian cancer: an exploratory analysis of a Gynecologic Oncology Group study. Gynecol Oncol 116(3):301–306CrossRef Chan JK, Tian C, Fleming GF, Monk BJ, Herzog TJ, Kapp DS et al (2010) The potential benefit of 6 vs, 3 cycles of chemotherapy in subsets of women with early-stage high-risk epithelial ovarian cancer: an exploratory analysis of a Gynecologic Oncology Group study. Gynecol Oncol 116(3):301–306CrossRef
8.
Zurück zum Zitat McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY et al (1996) Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group). Semin Oncol 23(5 Suppl 12):40–47PubMed McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY et al (1996) Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group). Semin Oncol 23(5 Suppl 12):40–47PubMed
9.
Zurück zum Zitat Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E et al (2000) Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 92(9):699–708CrossRef Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E et al (2000) Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 92(9):699–708CrossRef
10.
Zurück zum Zitat Piccart MJ, Bertelsen K, Stuart G, Cassidy J, Mangioni C, Simonsen E et al (2003) Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Int J Gynecol Cancer 13(Suppl 2):144–148CrossRef Piccart MJ, Bertelsen K, Stuart G, Cassidy J, Mangioni C, Simonsen E et al (2003) Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Int J Gynecol Cancer 13(Suppl 2):144–148CrossRef
11.
Zurück zum Zitat du Bois A, Luck HJ, Meier W, Adams HP, Mobus V, Costa S et al (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95(17):1320–1329CrossRef du Bois A, Luck HJ, Meier W, Adams HP, Mobus V, Costa S et al (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95(17):1320–1329CrossRef
12.
Zurück zum Zitat Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA 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(17):3194–3200CrossRef Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA 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(17):3194–3200CrossRef
13.
Zurück zum Zitat Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R et al (2004) Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96(22):1682–1691CrossRef Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R et al (2004) Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96(22):1682–1691CrossRef
14.
Zurück zum Zitat Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E et al (2011) Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol 29(27):3628–3635CrossRef Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E et al (2011) Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol 29(27):3628–3635CrossRef
15.
Zurück zum Zitat Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D et al (2009) Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 374(9698):1331–1338CrossRef Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D et al (2009) Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 374(9698):1331–1338CrossRef
16.
Zurück zum Zitat Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S et al (2014) Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 15(4):396–405CrossRef Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S et al (2014) Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 15(4):396–405CrossRef
17.
Zurück zum Zitat Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA et al (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335(26):1950–1955CrossRef Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA et al (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335(26):1950–1955CrossRef
18.
Zurück zum Zitat Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354(1):34–43CrossRef Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354(1):34–43CrossRef
19.
Zurück zum Zitat Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF et al (2001) 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, Journal of clinical oncology : official journal of the American Society of. Clin Oncol 19(4):1001–1007CrossRef Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF et al (2001) 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, Journal of clinical oncology : official journal of the American Society of. Clin Oncol 19(4):1001–1007CrossRef
20.
Zurück zum Zitat Walker JLBM, DiSilvestro P et al (2016) A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma, NCI-supplied agent: bevacizumab (NSC #704865, IND # 7921), A GOG/NRG trial (GOG 252), Abstract LBA6. Annual Meeting on Women’s Cancer, San Diego, 19–22. March 2016 Walker JLBM, DiSilvestro P et al (2016) A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma, NCI-supplied agent: bevacizumab (NSC #704865, IND # 7921), A GOG/NRG trial (GOG 252), Abstract LBA6. Annual Meeting on Women’s Cancer, San Diego, 19–22. March 2016
21.
Zurück zum Zitat Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E et al (2015) Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol 22(5):1570–1575CrossRef Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E et al (2015) Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol 22(5):1570–1575CrossRef
22.
Zurück zum Zitat van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM et al (2018) Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med 378(3):230–240CrossRef van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM et al (2018) Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med 378(3):230–240CrossRef
23.
Zurück zum Zitat Lim MC, Chang S‑J, Yoo HJ, Nam B‑H, Bristow R, Park S‑Y (2017) Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. J Clin Oncol 35(15_suppl):5520CrossRef Lim MC, Chang S‑J, Yoo HJ, Nam B‑H, Bristow R, Park S‑Y (2017) Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. J Clin Oncol 35(15_suppl):5520CrossRef
24.
Zurück zum Zitat Peng LH, Chen XY, Wu TX (2008) Topotecan for ovarian cancer. Cochrane Database Syst Rev 2:CD5589 Peng LH, Chen XY, Wu TX (2008) Topotecan for ovarian cancer. Cochrane Database Syst Rev 2:CD5589
25.
Zurück zum Zitat Ezcurdia L, Jovtis SL, Mickiewicz E, Temperley G, Rondinon M, Blajman C et al (1997) Paclitaxel in platinum-resistant ovarian cancer patients, Argentine Multicenter Taxol Group. Semin Oncol 24(5 Suppl 15):S15-53–S15-56 Ezcurdia L, Jovtis SL, Mickiewicz E, Temperley G, Rondinon M, Blajman C et al (1997) Paclitaxel in platinum-resistant ovarian cancer patients, Argentine Multicenter Taxol Group. Semin Oncol 24(5 Suppl 15):S15-53–S15-56
26.
Zurück zum Zitat Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H et al (1995) Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer 72(4):1016–1019CrossRef Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H et al (1995) Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer 72(4):1016–1019CrossRef
27.
Zurück zum Zitat Seewaldt VL, Greer BE, Cain JM, Figge DC, Tamimi HK, Brown WS et al (1994) Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Am J Obstet Gynecol 170(6):1666–1670 (discussion 70–71)CrossRef Seewaldt VL, Greer BE, Cain JM, Figge DC, Tamimi HK, Brown WS et al (1994) Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Am J Obstet Gynecol 170(6):1666–1670 (discussion 70–71)CrossRef
28.
Zurück zum Zitat Gynecologic Oncology G, Markman M, Blessing J, Rubin SC, Connor J, Hanjani P et al (2006) Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol 101(3):436–440CrossRef Gynecologic Oncology G, Markman M, Blessing J, Rubin SC, Connor J, Hanjani P et al (2006) Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol 101(3):436–440CrossRef
29.
Zurück zum Zitat Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan, Journal of clinical oncology : official journal of the American Society of. Clin Oncol 19(14):3312–3322CrossRef Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan, Journal of clinical oncology : official journal of the American Society of. Clin Oncol 19(14):3312–3322CrossRef
30.
Zurück zum Zitat Markman M, Kennedy A, Webster K, Peterson G, Kulp B, Belinson J (2000) Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 78(3 Pt 1):369–372CrossRef Markman M, Kennedy A, Webster K, Peterson G, Kulp B, Belinson J (2000) Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 78(3 Pt 1):369–372CrossRef
31.
Zurück zum Zitat Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD 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(19):2811–2818CrossRef Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD 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(19):2811–2818CrossRef
32.
Zurück zum Zitat Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T et al (2011) Topotecan Weekly Versus Conventional 5‑Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 29(2):242–248CrossRef Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T et al (2011) Topotecan Weekly Versus Conventional 5‑Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 29(2):242–248CrossRef
33.
Zurück zum Zitat Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB 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(9375):2099–2106CrossRef Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB 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(9375):2099–2106CrossRef
34.
Zurück zum Zitat Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ 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(29):4699–4707CrossRef Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ 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(29):4699–4707CrossRef
35.
Zurück zum Zitat Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM et al (2010) Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 28(19):3107–3114CrossRef Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM et al (2010) Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 28(19):3107–3114CrossRef
36.
Zurück zum Zitat Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA et al (2010) Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 28(20):3323–3329CrossRef Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA et al (2010) Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 28(20):3323–3329CrossRef
37.
Zurück zum Zitat Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M et al (2012) Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer 107(4):588–591CrossRef Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M et al (2012) Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer 107(4):588–591CrossRef
38.
Zurück zum Zitat Pfisterer J, Dean A, Baumann K, Rau J, Harter P, Joly F (2018) Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab (CD-BEV) vs, Carboplatin/Gemcitabine/Bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. ESMO 2018. Pfisterer J, Dean A, Baumann K, Rau J, Harter P, Joly F (2018) Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab (CD-BEV) vs, Carboplatin/Gemcitabine/Bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. ESMO 2018.
39.
Zurück zum Zitat Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S et al (2011) Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6–12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol 22(1):39–48CrossRef Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S et al (2011) Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6–12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol 22(1):39–48CrossRef
40.
Zurück zum Zitat Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U et al (2017) Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2,16, ENGOT-Ov1, GCIG Study. J Clin Oncol 35(29):3347–3353CrossRef Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U et al (2017) Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2,16, ENGOT-Ov1, GCIG Study. J Clin Oncol 35(29):3347–3353CrossRef
41.
Zurück zum Zitat Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H et al (2007) Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25(33):5180–5186CrossRef Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H et al (2007) Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25(33):5180–5186CrossRef
42.
Zurück zum Zitat Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI (2007) Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25(33:5165–5171CrossRef Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI (2007) Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25(33:5165–5171CrossRef
43.
Zurück zum Zitat Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV (2015) Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 139(1):10–16CrossRef Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV (2015) Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 139(1):10–16CrossRef
44.
Zurück zum Zitat Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039–2045CrossRef Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039–2045CrossRef
45.
Zurück zum Zitat Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL et al (2017) Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6):779–791CrossRef Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL et al (2017) Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6):779–791CrossRef
46.
Zurück zum Zitat Pfisterer J, Dean AP, Baumann K, Rau J, Harter P, Joly F et al (2018) 933OCarboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs, carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer: A prospective randomized phase III ENGOT/GCIG-Intergroup study (AGO study group, AGO-Austria, ANZGOG, GINECO, SGCTG). Ann Oncol 29(suppl_8):mdy285,142CrossRef Pfisterer J, Dean AP, Baumann K, Rau J, Harter P, Joly F et al (2018) 933OCarboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs, carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer: A prospective randomized phase III ENGOT/GCIG-Intergroup study (AGO study group, AGO-Austria, ANZGOG, GINECO, SGCTG). Ann Oncol 29(suppl_8):mdy285,142CrossRef
47.
Zurück zum Zitat Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK et al (2014) Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol 32(13):1309–1316CrossRef Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK et al (2014) Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol 32(13):1309–1316CrossRef
48.
Zurück zum Zitat Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G et al (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 32(13):1302–1308CrossRef Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G et al (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 32(13):1302–1308CrossRef
49.
Zurück zum Zitat Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496CrossRef Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496CrossRef
50.
Zurück zum Zitat Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E et al (2015) Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16(8):928–936CrossRef Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E et al (2015) Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16(8):928–936CrossRef
51.
Zurück zum Zitat Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483CrossRef Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483CrossRef
52.
Zurück zum Zitat Harter P, Hilpert F et al (2018) Therapy of ovarian cancer (OC) in Germany—Treatment characteristics and survival results of the QS OVAR. 62 Jahrestagung der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Berlin Harter P, Hilpert F et al (2018) Therapy of ovarian cancer (OC) in Germany—Treatment characteristics and survival results of the QS OVAR. 62 Jahrestagung der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Berlin
53.
Zurück zum Zitat Harter P, Hauke J, Heitz F, Reuss A, Kommoss S, Marme F et al (2017) Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS ONE 12(10):e186043CrossRef Harter P, Hauke J, Heitz F, Reuss A, Kommoss S, Marme F et al (2017) Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS ONE 12(10):e186043CrossRef
54.
Zurück zum Zitat Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376(9737):245–251CrossRef Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376(9737):245–251CrossRef
55.
Zurück zum Zitat Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K et al (2011) Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 12(9):852–861CrossRef Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K et al (2011) Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 12(9):852–861CrossRef
56.
Zurück zum Zitat Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J et al (2015) Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 33(3):244–250CrossRef Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J et al (2015) Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 33(3):244–250CrossRef
57.
Zurück zum Zitat Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366(15):1382–1392CrossRef Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366(15):1382–1392CrossRef
58.
Zurück zum Zitat Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al (2014) Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 15(8):852–861CrossRef Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al (2014) Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 15(8):852–861CrossRef
59.
Zurück zum Zitat Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM et al (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18(9):1274–1284CrossRef Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM et al (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18(9):1274–1284CrossRef
61.
Zurück zum Zitat Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A et al (2017) Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10106):1949–1961CrossRef Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A et al (2017) Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10106):1949–1961CrossRef
63.
Zurück zum Zitat Harter P, Sehouli J, Reuss A, Hasenburg A, Scambia G, Cibula D et al (2011) Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II, A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer 21(2):289–295CrossRef Harter P, Sehouli J, Reuss A, Hasenburg A, Scambia G, Cibula D et al (2011) Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II, A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer 21(2):289–295CrossRef
65.
Zurück zum Zitat Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348(3):203–213CrossRef Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348(3):203–213CrossRef
66.
Zurück zum Zitat Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL et al (2016) Weekly vs, Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. N Engl J Med 374(8):738–748CrossRef Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL et al (2016) Weekly vs, Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. N Engl J Med 374(8):738–748CrossRef
67.
Zurück zum Zitat Clamp A, McNeish I, Dean A, Gallardo D (2017) ICON8: A GCIG Phase III randomised trial evaluating weekly dose-dense chemotherapy integration in first-line Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Carcinoma (EOC) treatment: Results of primary progression free survival (pfs) analysis. ESMO 2017. Clamp A, McNeish I, Dean A, Gallardo D (2017) ICON8: A GCIG Phase III randomised trial evaluating weekly dose-dense chemotherapy integration in first-line Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Carcinoma (EOC) treatment: Results of primary progression free survival (pfs) analysis. ESMO 2017.
Metadaten
Titel
Medikamentöse Therapie des Ovarialkarzinoms in der Primär- und Rezidivsituation
verfasst von
Prof. Dr. med. Frederik Marmé
Philipp Harter
Beyhan Ataseven
Publikationsdatum
14.01.2019
Verlag
Springer Medizin
Erschienen in
Die Onkologie / Ausgabe 2/2019
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-018-0511-z

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