title: Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  Cbz at a dosage of 25mg/m(2) intravenously every 3 wk combined with 5mg of oral prednisone twice a day.
  
  
  METHODS
  Treatment-associated toxicity was the primary study end point; progression-free and overall survival were secondary end points. A descriptive statistical analysis was performed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, RWTH University Aachen, Aachen, Germany. aheidenreich@ukaachen.de
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Scholz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rogenhofer
authors.forename: Christian
authors.initials: C
authors.lastname: Arsov
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gschwend
authors.forename: Manfred
authors.initials: M
authors.lastname: Wirth
authors.forename: Ursula
authors.initials: U
authors.lastname: Steiner
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Elmar
authors.initials: E
authors.lastname: Heinrich
authors.forename: Lutz
authors.initials: L
authors.lastname: Trojan
authors.forename: Björn
authors.initials: B
authors.lastname: Volkmer
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Honecker
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Burkhard
authors.initials: B
authors.lastname: Otremba
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ecstein-Fraisse
authors.forename: David
authors.initials: D
authors.lastname: Pfister
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D057176:Compassionate Use Trials; D018572:Disease-Free Survival; D000077143:Docetaxel; D005334:Fever / Q000139:chemically induced / Q000150:complications; D005858:Germany; D006801:Humans; D007610:Kallikreins; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D011241:Prednisone