Cabazitaxel Plus Prednisone for Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel: Results from the German Compassionate-use Programme

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• 作者：Axel Heidenreich^a ; ^{aheidenreich@ukaachen.de} ; Hans-Jö ; rg Scholz^b ; Sebastian Rogenhofer^c ; Christian Arsov^d ; Margitta Retz^e ; Stefan C. M&uuml ; ller^c ; Peter Albers^d ; J&uuml ; rgen Gschwend^e ; Manfred Wirth^f ; Ursula Steiner^g ; Kurt Miller^g ; Elmar Heinrich^h ; Lutz Trojan^h ; Bjö ; rn Volkmerⁱ ; Friedhelm Honecker^j ; Carsten Bokemeyer^j ; Bastian Keck^k ; Burkhard Otremba^l ; Evelyne Ecstein-Fraisse^m ; David Pfister^a
• 关键词：Chemotherapy ; Castration-resistant prostate cancer ; Docetaxel ; Mitoxantrone
• 刊名：European Urology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：63
• 期：6
• 页码：977-982
• 全文大小：193 K

文摘

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 ¡À 10.8 cycles (range: 6-69 cycles) of docetaxel with a mean cumulative dose of 970.9 mg/m²; 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 25 mg/m² intravenously every 3 wk combined with 5 mg 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 ¡À 2.2 cycles of Cbz and a mean cumulative dose of 160.3 ¡À 51.5 mg/m². 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.