Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme

Eur J Cancer. 2014 Apr;50(6):1090-9. doi: 10.1016/j.ejca.2014.01.006. Epub 2014 Jan 31.

Abstract

Background: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access programmes (EAPs) were established worldwide, allowing access to cabazitaxel before its commercial availability. Preliminary results of the European CUP/EAP, focusing on the elderly population (aged > or =70 years), are reported.

Patients and methods: Enrolled patients with progressive mCRPC received cabazitaxel (25 mg/m2) plus 10mg oral prednisone/prednisolone every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. Safety was analysed by age group (<70, 70-74 and > or =75 years). The influence of selected variables on grade > or =3 neutropenia and/or neutropenic complications was analysed in multivariate analysis.

Results: 746 men were enrolled (<70 years, n=421; 70-74, n=180, > or =75 years, n=145). Number of cabazitaxel cycles, dose reductions for any cause, dose delays possibly related to cabazitaxel adverse events, and tolerability were similar in the three age groups. Prophylactic granulocyte colony-stimulating factor (G-CSF) use was more common in men aged > or =0 years. In multivariate analysis, age > or =75 years, treatment cycle 1, and neutrophil count <4000/mm3 before cabazitaxel injection were associated with increased risk of developing grade > or =3 neutropenia and/or neutropenic complications. Prophylactic use of G-CSF at a given cycle significantly reduced this risk by 30% (odds ratio 0.70, p=0.04).

Conclusion: The results suggest that cabazitaxel has a manageable safety profile in everyday clinical practice. Prophylactic use of G-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel.

Keywords: Cabazitaxel; Elderly; Granulocyte colony-stimulating factor; Metastatic castration-resistant prostate cancer; Neutropenia; Safety; Senior men; Supportive care.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Compassionate Use Trials*
  • Diarrhea / chemically induced
  • Disease Progression
  • Drug Administration Schedule
  • Europe
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nausea / chemically induced
  • Neoplasm Metastasis
  • Neutropenia / chemically induced
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Taxoids
  • cabazitaxel
  • Prednisolone
  • Prednisone