دورية أكاديمية

Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure.

التفاصيل البيبلوغرافية
العنوان: Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure.
المؤلفون: Meulenbeld HJ, Bleuse JP, Vinci EM, Raymond E, Vitali G, Santoro A, Dogliotti L, BERARDI, ROSSANA, Cappuzzo F, Tagawa ST, Sternberg CN, Jannuzzo MG, Mariani M, Petroccione A, de Wit R.
المساهمون: Meulenbeld, Hj, Bleuse, Jp, Vinci, Em, Raymond, E, Vitali, G, Santoro, A, Dogliotti, L, Berardi, Rossana, Cappuzzo, F, Tagawa, St, Sternberg, Cn, Jannuzzo, Mg, Mariani, M, Petroccione, A, de Wit, R.
سنة النشر: 2012
المجموعة: Università Politecnica delle Marche: IRIS
الوصف: Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Since their discovery aurora kinases have been identified as a potential target in anticancer therapy and currently many aurora-selective small molecule kinase inhibitors are in development. Aurora kinases play an essential role as key mitotic regulators and are frequently overexpressed in prostate cancer. In vivo data in the transgenic mouse prostate carcinoma model revealed tumour regressions of >80% in three out of 16 animals and disease stabilizations in 10 out of 16 animals treated with danusertib. Two phase I dose escalation studies with danusertib in patients with advanced solid tumours were performed, which established two doses and schedules for phase II studies. However, the preliminary data of the available phase II studies with danusertib in solid tumours showed limited activity. Danusertib may yield more activity in the treatment of leukaemias than in solid tumours. Danusertib is generally well tolerated with neutropenia as the main dose limiting toxicity. This phase II study determined the efficacy and toxicity of danusertib administered intravenously over two different dosing schedules in patients with metastatic castration-resistant prostate cancer (CRPC) with progressive disease after docetaxel-based treatment. Danusertib showed in vivo antitumour activity in prostate cancer models and clinically relevant disease stabilizations were observed in several patients with solid tumours in phase I studies. However, our study revealed that monotherapy with danusertib, although well tolerated, showed only limited activity in the treatment of patients with CRPC. In view of the new advances in the treatment of patients with CRPC and the negative result of our study it is unlikely that danusertib will be further explored for the treatment of patients with CRPC. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization to ...
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/22928785; info:eu-repo/semantics/altIdentifier/wos/WOS:000315160900014; journal:BJU INTERNATIONAL; http://hdl.handle.net/11566/82166Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84871613362
الإتاحة: http://hdl.handle.net/11566/82166Test
رقم الانضمام: edsbas.3EFB7613
قاعدة البيانات: BASE