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

Eur Urol. 2013 Jun;63(6):977-82. doi: 10.1016/j.eururo.2012.08.058. Epub 2012 Sep 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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