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.

Základní údaje

Originální název

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

Autoři

DE BONO, J. S. (826 Velká Británie a Severní Irsko, garant), S. OUDARD (250 Francie), M. OZGUROGLU (792 Turecko), S. HANSEN (208 Dánsko), J. P. MACHIELS (56 Belgie), Ivo KOCÁK (203 Česká republika, domácí), G. GRAVIS (250 Francie), I. BODROGI (348 Maďarsko), M. J. MACKENZIE (124 Kanada), L. SHEN (840 Spojené státy), M. ROESSNER (840 Spojené státy), S. GUPTA (840 Spojené státy) a A. O. SARTOR (840 Spojené státy)

Vydání

Lancet, 2010, 0140-6736

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 33.633

Kód RIV

RIV/00216224:14110/10:00051758

Organizační jednotka

Lékařská fakulta

DOI

UT WoS

000282915700031

Klíčová slova anglicky

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

Příznaky

Mezinárodní význam
Změněno: 12. 4. 2012 14:36, Mgr. Michal Petr

Anotace

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.