title: 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial.
abstract: BACKGROUND
  Docetaxel administered every 3 weeks is a standard treatment for castration-resistant advanced prostate cancer. We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer, and did a prospective, multicentre, randomised, phase 3 study to compare efficacy and safety.
  
  
  METHODS
  Eligible patients had advanced prostate cancer (metastasis, a prostate-specific-antigen test result of more than 10·0 ng/mL, and WHO performance status score of 0-2), had received no chemotherapy (except with estramustine), had undergone surgical or chemical castration, and had been referred to a treatment centre in Finland, Ireland, or Sweden. Enrolment and treatment were done between March 1, 2004, and May 31, 2009. Randomisation was done centrally and stratified by centre and WHO performance status score of 0-1 vs 2. Patients were assigned 75 mg/m(2) docetaxel intravenously on day 1 of a 3-week cycle, or 50 mg/m(2) docetaxel intravenously on days 1 and 15 of a 4-week cycle. 10 mg oral prednisolone was administered daily to all patients. The primary endpoint was time to treatment failure (TTTF). We assessed data in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00255606.
  
  
  RESULTS
  177 patients were randomly assigned to the 2-weekly docetaxel group and 184 to the 3-weekly group. 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis. The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration (5·6 months, 95% CI 5·0-6·2 vs 4·9 months, 4·5-5·4; hazard ratio 1·3, 95% CI 1·1-1·6, p=0·014). Grade 3-4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group, including neutropenia (93 [53%] vs 61 [36%]), leucopenia (51 [29%] vs 22 [13%]), and febrile neutropenia (25 [14%] vs six [4%]). Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks (43 [24%] vs 11 [6%], p=0·002).
  
  
  CONCLUSIONS
  Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated.
  
  
  BACKGROUND
  Sanofi.
authors.affiliation: Department of Oncology, Tampere University Hospital, Tampere, Finland. Pirkko-Liisa.Kellokumpu-Lehtinen@uta.fi
authors.forename: Pirkko-Liisa
authors.initials: PL
authors.lastname: Kellokumpu-Lehtinen
authors.forename: Ulrika
authors.initials: U
authors.lastname: Harmenberg
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Ray
authors.initials: R
authors.lastname: McDermott
authors.forename: Petteri
authors.initials: P
authors.lastname: Hervonen
authors.forename: Claes
authors.initials: C
authors.lastname: Ginman
authors.forename: Marjaana
authors.initials: M
authors.lastname: Luukkaa
authors.forename: Paul
authors.initials: P
authors.lastname: Nyandoto
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: John
authors.initials: J
authors.lastname: McCaffrey
authors.forename: Raija
authors.initials: R
authors.lastname: Asola
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Laestadius
authors.forename: Tiina
authors.initials: T
authors.lastname: Tasmuth
authors.forename: Katinka
authors.initials: K
authors.lastname: Sandberg
authors.forename: Maccon
authors.initials: M
authors.lastname: Keane
authors.forename: Ilari
authors.initials: I
authors.lastname: Lehtinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Luukkaala
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004333:Drug Administration Routes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel