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Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration

Tyrrell, Chris J. ; Iversen, Peter ; Tammela, Teuvo ; Anderson, John ; Björk, Thomas LU ; Kaisary, Amir V. and Morris, Thomas (2006) In BJU International 98(3). p.563-572
Abstract
OBJECTIVE To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of > 150 mg to patients with locally advanced (MO) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS Systemic exposure to bicalutamide stabilised at a dose of approximate to 300 mg, as determined by pharmacokinetic analysis. The... (More)
OBJECTIVE To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of > 150 mg to patients with locally advanced (MO) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS Systemic exposure to bicalutamide stabilised at a dose of approximate to 300 mg, as determined by pharmacokinetic analysis. The tolerability of high doses of bicalutamide was similar to that of the 150 mg dose, with no increase in the incidence of adverse events. Patients receiving bicalutamide had early increases in the mean levels of oestradiol, testosterone and luteinizing hormone, which were maintained throughout the study. Levels of these hormones rapidly decreased in the castration group and remained low. From baseline (first day of treatment) to 12 weeks there was an equivalent reduction in prostate-specific antigen (PSA) levels across all four groups. At a median follow-up of 5 years, there was no significant survival difference between patients who received bicalutamide and those who received castration, either in M0 or M1 disease. CONCLUSION The low median PSA level (180 ng/mL) of patients with M1 disease might account for the lack of survival difference between the treatment groups. Further studies are needed to assess whether high-dose bicalutamide monotherapy can provide equivalent efficacy to castration in patients with M1 prostate cancer. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
survival, tolerability, prostate cancer, bicalutamide, monotherapy, pharmacokinetics
in
BJU International
volume
98
issue
3
pages
563 - 572
publisher
Wiley-Blackwell
external identifiers
  • wos:000240199500020
  • pmid:16771791
  • scopus:33746911141
ISSN
1464-4096
DOI
10.1111/j.1464-410X.2006.06275.x
language
English
LU publication?
yes
id
9efa3fdb-a014-45cb-b870-4ce1e965e86a (old id 686214)
date added to LUP
2016-04-01 12:01:27
date last changed
2021-01-12 03:23:58
@article{9efa3fdb-a014-45cb-b870-4ce1e965e86a,
  abstract     = {OBJECTIVE To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of > 150 mg to patients with locally advanced (MO) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS Systemic exposure to bicalutamide stabilised at a dose of approximate to 300 mg, as determined by pharmacokinetic analysis. The tolerability of high doses of bicalutamide was similar to that of the 150 mg dose, with no increase in the incidence of adverse events. Patients receiving bicalutamide had early increases in the mean levels of oestradiol, testosterone and luteinizing hormone, which were maintained throughout the study. Levels of these hormones rapidly decreased in the castration group and remained low. From baseline (first day of treatment) to 12 weeks there was an equivalent reduction in prostate-specific antigen (PSA) levels across all four groups. At a median follow-up of 5 years, there was no significant survival difference between patients who received bicalutamide and those who received castration, either in M0 or M1 disease. CONCLUSION The low median PSA level (180 ng/mL) of patients with M1 disease might account for the lack of survival difference between the treatment groups. Further studies are needed to assess whether high-dose bicalutamide monotherapy can provide equivalent efficacy to castration in patients with M1 prostate cancer.},
  author       = {Tyrrell, Chris J. and Iversen, Peter and Tammela, Teuvo and Anderson, John and Björk, Thomas and Kaisary, Amir V. and Morris, Thomas},
  issn         = {1464-4096},
  language     = {eng},
  number       = {3},
  pages        = {563--572},
  publisher    = {Wiley-Blackwell},
  series       = {BJU International},
  title        = {Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration},
  url          = {http://dx.doi.org/10.1111/j.1464-410X.2006.06275.x},
  doi          = {10.1111/j.1464-410X.2006.06275.x},
  volume       = {98},
  year         = {2006},
}