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

TY - JOUR

T1 - Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme.

AU - Heidenreich, Axel

AU - Scholz, Hans-Jörg

AU - Rogenhofer, Sebastian

AU - Arsov, Christian

AU - Retz, Margitta

AU - Müller, Stefan C

AU - Albers, Peter

AU - Gschwend, Jürgen

AU - Wirth, Manfred

AU - Steiner, Ursula

AU - Miller, Kurt

AU - Heinrich, Elmar

AU - Trojan, Lutz

AU - Volkmer, Björn

AU - Honecker, Friedemann Ulrich

AU - Bokemeyer, Carsten

AU - Keck, Bastian

AU - Otremba, Burkhard

AU - Ecstein-Fraisse, Evelyne

AU - Pfister, David

N1 - Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Anemia

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Compassionate Use Trials

KW - Disease-Free Survival

KW - Fever

KW - Germany

KW - Humans

KW - Kallikreins

KW - Male

KW - Middle Aged

KW - Neutropenia

KW - Prednisone

KW - Prostate-Specific Antigen

KW - Prostatic Neoplasms

KW - Taxoids

KW - Thrombocytopenia

KW - Treatment Failure

KW - Treatment Outcome

U2 - 10.1016/j.eururo.2012.08.058

DO - 10.1016/j.eururo.2012.08.058

M3 - SCORING: Journal article

C2 - 23116658

VL - 63

SP - 977

EP - 982

JO - EUR UROL

JF - EUR UROL

SN - 0302-2838

IS - 6

M1 - 6

ER -