J 2010

Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

DE BONO, J. S., S. OUDARD, M. OZGUROGLU, S. HANSEN, J. P. MACHIELS et. al.

Basic information

Original name

Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

Authors

DE BONO, J. S. (826 United Kingdom of Great Britain and Northern Ireland, guarantor), S. OUDARD (250 France), M. OZGUROGLU (792 Turkey), S. HANSEN (208 Denmark), J. P. MACHIELS (56 Belgium), Ivo KOCÁK (203 Czech Republic, belonging to the institution), G. GRAVIS (250 France), I. BODROGI (348 Hungary), M. J. MACKENZIE (124 Canada), L. SHEN (840 United States of America), M. ROESSNER (840 United States of America), S. GUPTA (840 United States of America) and A. O. SARTOR (840 United States of America)

Edition

Lancet, 2010, 0140-6736

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 33.633

RIV identification code

RIV/00216224:14110/10:00051758

Organization unit

Faculty of Medicine

DOI

UT WoS

000282915700031

Keywords in English

EVERY 3 WEEKS; SOLID TUMORS; END-POINTS; CHEMOTHERAPY; ESTRAMUSTINE; TAXANE; PAIN

Tags

International impact
Změněno: 12/4/2012 14:36, Mgr. Michal Petr

Abstract

V originále

Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment. Methods We undertook an open-label randomised phase 3 trial in men with metastatic castration-resistant prostate cancer who had received previous hormone therapy, but whose disease had progressed during or after treatment with a docetaxel-containing regimen. Participants were treated with 10 mg oral prednisone daily, and were randomly assigned to receive either 12 mg/m(2) mitoxantrone intravenously over 15-30 min or 25 mg/m(2) cabazitaxel intravenously over 1 h every 3 weeks. The random allocation schedule was computer-generated; patients and treating physicians were not masked to treatment allocation, but the study team was masked to the data analysis. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and safety. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, NCT00417079. Findings 755 men were allocated to treatment groups (377 mitoxantrone, 378 cabazitaxel) and were included in the intention-to-treat analysis. At the cutoff for the final analysis (Sept 25, 2009), median survival was 15.1 months (95% CI 14.1-16.3) in the cabazitaxel group and 12.7 months (11.6-13.7) in the mitoxantrone group. The hazard ratio for death of men treated with cabazitaxel compared with those taking mitoxantrone was 0.70 (95% CI 0.59-0.83, p<0.0001). Median progression-free survival was 2.8 months (95% CI 2.4-3.0) in the cabazitaxel group and 1.4 months (1.4-1.7) in the mitoxantrone group (HR 0.74, 0.64-0.86, p<0.0001). The most common clinically significant grade 3 or higher adverse events were neutropenia (cabazitaxel, 303 [82%] patients vs mitoxantrone, 215 [58%]) and diarrhoea (23 [6%] vs one [<1%]). 28 (8%) patients in the cabazitaxel group and five (1%) in the mitoxantrone group had febrile neutropenia. Interpretation Treatment with cabazitaxel plus prednisone has important clinical antitumour activity, improving overall survival in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy.