Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme.

Abstract

BACKGROUND:

Cabazitaxel (Cbz) is an approved second-line treatment in metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy with a significant survival benefit compared with mitoxantrone. However, grade 3/4 toxicities were reported in 82% of patients.

OBJECTIVE:

To report on the safety results of mCRPC patients treated within a compassionate-use programme in Germany.

DESIGN, SETTING, AND PARTICIPANTS:

A total of 111 patients with a mean age of 67.9 yr (range: 49-81 yr) and progressive mCRPC were included. Patients had received a mean number of 12.7 ± 10.8 cycles (range: 6-69 cycles) of docetaxel with a mean cumulative dose of 970.9 mg/m(2); mean time from last docetaxel application to progression was 6.95 mo (range: 2-54 mo). Of the patients, 31.5% progressed by prostate-specific antigen (PSA) increase only; the remainder had a combination of PSA increase and clinical progression.

INTERVENTION:

Cbz at a dosage of 25mg/m(2) intravenously every 3 wk combined with 5mg of oral prednisone twice a day.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Treatment-associated toxicity was the primary study end point; progression-free and overall survival were secondary end points. A descriptive statistical analysis was performed.

RESULTS AND LIMITATIONS:

Patients received a mean number of 6.5 ± 2.2 cycles of Cbz and a mean cumulative dose of 160.3 ± 51.5mg/m(2). Grade 3 and 4 treatment-emergent adverse events were recorded in 34 patients (30.6%) and 18 patients (16.2%), respectively. Grade 3/4 anaemia, neutropenia, and thrombocytopenia were reported in 4.5%, 7.2%, and 0.9% of the patients, respectively. Neutropenic fever was reported in 1.8% of the patients. Grade 3/4 gastrointestinal toxicity was identified in 4.5% of the patients. Three patients died because of Cbz-related toxicity. Granulocyte colony-stimulating growth factors were used in 17.1% of patients. The limitations are due to the nonrandomised nature of the trial.

CONCLUSIONS:

Treatment with Cbz is tolerable and is associated with a low incidence of serious adverse events in a real-world patient population with CRPC. The outcome of serious adverse events can be minimised with proactive treatment management and conscientious monitoring.

• Authors: Axel Heidenreich, Hans-Jörg Scholz, Sebastian Rogenhofer, Christian Arsov, Margitta Retz, Stefan C Müller, Peter Albers, Jürgen Gschwend, Manfred Wirth, Ursula Steiner, Kurt Miller, Elmar Heinrich, Lutz Trojan, Björn Volkmer, Friedhelm Honecker, Carsten Bokemeyer, Bastian Keck, Burkhard Otremba, Evelyne Ecstein-Fraisse, David Pfister
• Journal: European urology (Eur Urol) Vol. 63 Issue 6 Pg. 977-82 (Jun 2013) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 23116658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Taxoids
• Docetaxel
• cabazitaxel
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen
• Prednisone

Topics

• Aged
• Aged, 80 and over
• Anemia (chemically induced)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Compassionate Use Trials
• Disease-Free Survival
• Docetaxel
• Fever (chemically induced, complications)
• Germany
• Humans
• Kallikreins
• Male
• Middle Aged
• Neutropenia (chemically induced, complications)
• Prednisone (administration & dosage)
• Prostate-Specific Antigen
• Prostatic Neoplasms (drug therapy, mortality, pathology)
• Taxoids (administration & dosage)
• Thrombocytopenia (chemically induced)
• Treatment Failure
• Treatment Outcome