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


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).


CONCLUSIONS
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.
RWTH Aachen University, Department of Urology, Aachen, Germany. Electronic address: aheidenreich@ukaachen.de.
Axel
A
Heidenreich
Ospedaliero San Donato, Department of Oncology, Arezzo, Italy.
Sergio
S
Bracarda
Cardiff University, Department of Oncology, Wales, UK.
Malcolm
M
Mason
Hacettepe University, Department of Urology, Ankara, Turkey.
Haluk
H
Ozen
Herlev University Hospital, Department of Oncology, Herlev, Denmark.
Lisa
L
Sengelov
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, Netherlands.
Inge
I
Van Oort
Larissa University Hospital, Department of Oncology, Larissa, Greece.
Christos
C
Papandreou
Oslo University Hospital, Department of Oncology, Oslo, Norway.
Sophie
S
Fossa
Sanofi, Statistics, Paris, France.
Simon
S
Hitier
Fundación Instituto Valenciano De Oncología, Department of Oncology, Valencia, Spain.
Miguel Angel
MA
Climent
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D057176:Compassionate Use Trials; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D004334:Drug Administration Schedule; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D043823:Taxoids; C552428:cabazitaxel; D011239:Prednisolone; D011241:Prednisone
Cabazitaxel; Elderly; Granulocyte colony-stimulating factor; Metastatic castration-resistant prostate cancer; Neutropenia; Safety; Senior men; Supportive care