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)

Abstract

ObjectiveIn 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.MethodsPatients 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.Results250 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.ConclusionsGiven 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-016-2307-0) contains supplementary material, which is available to authorized users.

Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives

“…Treosulfan, a water-soluble dihydroxy derivative of busulfan, is authorized in some European countries for the intravenous or oral treatment of advanced ovarian cancer. The intravenous regimen usually relies on drug doses of 5–8 g/m 2 administered every 3–4 weeks [ 1 – 3 ]. Moreover, for the last 17 years, high-dose treosulfan has been investigated worldwide as a myeloablative agent in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT).…”

Effect of combination of Yiqi Jianpi Yangxue Decoction and chemotherapy on quality of life and adverse reactions of patients with recurrent ovarian cancer

“…Ovarian cancer (OC), a malignant tumor in the female reproductive organs, may occur at any age, but it is seen mostly in women over 50 years old [1][2][3]. Clinical medical statistics indicate that the incidence of OC ranks third, while its mortality ranks first among gynecological malignancies in China [4].…”

In Vitro Study of the Enzymatic and Nonenzymatic Conjugation of Treosulfan with Glutathione

“…Treosulfan (dihydroxybusulfan, Fig. 1) is licensed in several European countries for the treatment of advanced ovarian carcinoma [1]. Unlike busulfan, treosulfan is a prodrug in which biological activity relies upon a nonenzymatic pH-dependent conversion to DNA alkylating epoxides—(2 S ,3 S )-1,2-epoxybutane-3,4-diol 4-methanesulfonate (EBDM) and (2 S ,3 S )-1,2:3,4-diepoxybutane (DEB) [2–4].…”