The online version of this article (doi:10.1007/s00432-016-2307-0) contains supplementary material, which is available to authorized users.
Results of this study were presented at the IGCS 2014 in Melbourne.
iOMEDICO Clinical Research, Freiburg, Germany is associated to University Hospital Essen, West German Cancer Center, Clinic for Internal Medicine (Tumor Research), Essen, Germany.
In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC.
Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life.
250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred.
Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.
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 30:2039–2045. doi: 10.1200/JCO.2012.42.0505CrossRefPubMedPubMedCentral
de Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R, EUROCARE-5 Working Group (2014) Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE–5-a population-based study. Lancet Oncol 15(1):23–34. doi: 10.1016/S1470-2045(13)70546-1CrossRefPubMed
Liu G, Franssen E, Fitch MI, Warner E (1997) Patient preferences for oral versus intravenous palliative chemotherapy. JCO 15:110–115
Mahner S, Oskay-Özcelik G, Heidrich-Lorsbach E, Fuxius S, Sommer H, Klare P et al (2012) A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis. J Cancer Res Clin Oncol 138:1413–1419. doi: 10.1007/s00432-012-1221-3CrossRefPubMedPubMedCentral
Meden H, Wittkop Y, Kuhn W (1997) Maintenance chemotherapy with oral treosulfan following first-line treatment in patients with advanced ovarian cancer: feasibility and toxicity. Anticancer Res 17:2221–2223 PubMed
Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M et al (2009) 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). Gynecol Oncol 114:199–205. doi: 10.1016/j.ygyno.2009.04.026CrossRefPubMed
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):3323–3329. doi: 10.1200/JCO.2009.25.7519CrossRefPubMed
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):1302–1308. doi: 10.1200/JCO.2013.51.4489CrossRefPubMed
Reed NS, Poole CJ, Coleman R, Parkin D, Graham JD, Kaye SB et al (2006) A randomised comparison of treosulfan and carboplatin in patients with ovarian cancer: a study by the Scottish Gynaecological Cancer Trials Group (SGCTG). Eur J Cancer 42(2):179–185. doi: 10.1016/j.ejca.2005.09.022CrossRefPubMed
Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P et al (2008) Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 26(19):3176–3182. doi: 10.1200/JCO.2007.15.1258CrossRefPubMed
- A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO)
Ingo Bernhard Runnebaum
Hans Werner Tessen
Mustafa Zelal Muallem
Michael Patrick Lux
- Springer Berlin Heidelberg
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II