Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR) - PubMed (original) (raw)
Clinical Trial
. 2009 Aug;114(2):199-205.
doi: 10.1016/j.ygyno.2009.04.026. Epub 2009 May 14.
Affiliations
- PMID: 19446314
- DOI: 10.1016/j.ygyno.2009.04.026
Clinical Trial
Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR)
Werner Meier et al. Gynecol Oncol. 2009 Aug.
Abstract
Objective: Effective therapies with a low rate of side effects are warranted in the 2nd-line setting in ovarian cancer. Both topotecan and the alkylating agent treosulfan have demonstrated efficacy in this patient group and are broadly used in Germany. Therefore, we started a prospectively randomized phase III trial comparing these two drugs in early recurrent ovarian cancer.
Methods: Patients having relapsed after platinum-taxane therapy were randomized to receive either topotecan or treosulfan. Stratification depended on platinum sensitivity (stratum 1: up to 6 months after primary chemotherapy, stratum 2: 6 to 12 months).
Results: A total of 274 patients were treated either with topotecan (136 patients) or treosulfan (138). Hematologic toxicity was significantly more frequent with topotecan but without severe clinical consequences. Non hematologic toxicity was similar in both study arms. Overall survival was significantly longer with topotecan (p=0.0023), with a median of 55.0 weeks versus 41.0 weeks as well as progression-free survival (p=0.0020) with a median of 23.1 weeks versus 12.7 weeks. Similar results were found for stratum 2 subgroup. Overall response rate was 27.5% for topotecan and 16.0% for treosulfan (p=0.0307). In stratum 1 progression-free survival was 18.1 weeks for topotecan and 9.4 weeks for treosulfan (p=0.0476), but there was no difference in overall survival in this prognostic poor subgroup.
Conclusions: This randomized phase III trial could detect superiority of topotecan versus treosulfan in patients with recurrent disease after platinum-paclitaxel combination therapy. Our experience indicates that optimization of systemic treatment could improve outcome even in this poor prognostic subgroup of patients with relapsed ovarian cancer.
Similar articles
- Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO.
Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, Bourgeois H, Meier W, Costa S, Blohmer JU, Lortholary A, Olbricht S, Stähle A, Jackisch C, Hardy-Bessard AC, Möbus V, Quaas J, Richter B, Schröder W, Geay JF, Lück HJ, Kuhn W, Meden H, Nitz U, Pujade-Lauraine E; AGO-OVAR; GINECO. Pfisterer J, et al. J Natl Cancer Inst. 2006 Aug 2;98(15):1036-45. doi: 10.1093/jnci/djj296. J Natl Cancer Inst. 2006. PMID: 16882940 Clinical Trial. - Medical therapy of advanced malignant epithelial tumours of the ovary.
Colombo N, Parma G, Bocciolone L, Franchi D, Sideri M, Maggioni A. Colombo N, et al. Forum (Genova). 2000 Oct-Dec;10(4):323-32. Forum (Genova). 2000. PMID: 11535983 Review. - Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens.
du Bois A, Weber B, Rochon J, Meier W, Goupil A, Olbricht S, Barats JC, Kuhn W, Orfeuvre H, Wagner U, Richter B, Lueck HJ, Pfisterer J, Costa S, Schroeder W, Kimmig R, Pujade-Lauraine E; Arbeitsgemeinschaft Gynaekologische Onkologie; Ovarian Cancer Study Group; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. du Bois A, et al. J Clin Oncol. 2006 Mar 1;24(7):1127-35. doi: 10.1200/JCO.2005.03.2938. J Clin Oncol. 2006. PMID: 16505432 Clinical Trial. - Carboplatin/paclitaxel versus cisplatin/paclitaxel as first-line chemotherapy in advanced ovarian cancer: an interim analysis of a randomized phase III trial of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.
du Bois A, Lück HJ, Meier W, Möbus V, Costa S, Richter B, Warm M, Bauknecht T, Schröder W, Olbricht S, Nitz U, Jackisch C. du Bois A, et al. Semin Oncol. 1997 Oct;24(5 Suppl 15):S15-44-S15-52. Semin Oncol. 1997. PMID: 9346222 Clinical Trial. - New options for the treatment of advanced ovarian cancer.
Dunton CJ. Dunton CJ. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-2-S5-11. Semin Oncol. 1997. PMID: 9122739 Review.
Cited by
- Chemotherapy: Topotecan or treosulfan--that is the question.
Markman M. Markman M. Nat Rev Clin Oncol. 2009 Oct;6(10):559-60. doi: 10.1038/nrclinonc.2009.144. Nat Rev Clin Oncol. 2009. PMID: 19786996 No abstract available. - Cost-utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model.
Lee HY, Yang BM, Hong JM, Lee TJ, Kim BG, Kim JW, Kim YT, Kim YM, Kang S. Lee HY, et al. Clinicoecon Outcomes Res. 2013 Jul 3;5:297-307. doi: 10.2147/CEOR.S42170. Print 2013. Clinicoecon Outcomes Res. 2013. PMID: 23869171 Free PMC article. - Overall survival and post-progression survival are potent endpoint in phase III trials of second/third-line chemotherapy for advanced or recurrent epithelial ovarian cancer.
Shimokawa M, Kogawa T, Shimada T, Saito T, Kumagai H, Ohki M, Kaku T. Shimokawa M, et al. J Cancer. 2018 Feb 16;9(5):872-879. doi: 10.7150/jca.17664. eCollection 2018. J Cancer. 2018. PMID: 29581765 Free PMC article. - Cyclophosphamide causes osteoporosis in C57BL/6 male mice: suppressive effects of cyclophosphamide on osteoblastogenesis and osteoclastogenesis.
Zhao D, Wang C, Zhao Y, Shu B, Jia Y, Liu S, Wang H, Chang J, Dai W, Lu S, Shi Q, Yang Y, Zhang Y, Wang Y. Zhao D, et al. Oncotarget. 2017 Sep 18;8(58):98163-98183. doi: 10.18632/oncotarget.21000. eCollection 2017 Nov 17. Oncotarget. 2017. PMID: 29228681 Free PMC article. - A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis.
Mahner S, Oskay-Özcelik G, Heidrich-Lorsbach E, Fuxius S, Sommer H, Klare P, Belau A, Ruhmland B, Heuser T, Kölbl H, Markmann S, Sehouli J. Mahner S, et al. J Cancer Res Clin Oncol. 2012 Aug;138(8):1413-9. doi: 10.1007/s00432-012-1221-3. Epub 2012 Apr 15. J Cancer Res Clin Oncol. 2012. PMID: 22526159 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical