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)

Autor: Radoslav Chekerov, Desislava Dimitrova, Jalid Sehouli, Mustafa Zelal Muallem, Ingo B. Runnebaum, Michael P. Lux, Hans Werner Tessen, Oliver Tome, Oumar Camara, Beate Rautenberg, Tanja Trarbach, Gerald Gitsch
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Oncology
Adult
Cancer Research
medicine.medical_specialty
Treosulfan
Drug-Related Side Effects and Adverse Reactions
medicine.medical_treatment
Original Article – Clinical Oncology
Administration
Oral
030226 pharmacology & pharmacy
Disease-Free Survival
Drug Administration Schedule
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Ovarian cancer
Internal medicine
Clinical endpoint
Medicine
Humans
Busulfan
Oral versus intravenous
Aged
Aged
80 and over
Ovarian Neoplasms
Chemotherapy
Hematology
Leukopenia
business.industry
General Medicine
Middle Aged
medicine.disease
Surgery
Treatment Outcome
030220 oncology & carcinogenesis
Quality of Life
Administration
Intravenous
Female
medicine.symptom
Neoplasm Recurrence
Local
business
Recurrent
medicine.drug
Zdroj: Journal of Cancer Research and Clinical Oncology
ISSN: 1432-1335
0171-5216
Popis: Objective 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. Methods 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1007/s00432-016-2307-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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