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Maximum androgen blockade in 1996
1Department of Urology, CHU Bichat, Paris, France.
Objectives:
To review the current status of maximal androgen blockade (MAB) in the treatment of patients with prostate cancer.
Introduction:
Ten years after its launch, the concept of MAB remains open to many questions regarding its modalities and efficacy. Although more than 5,000 patients with metastatic prostate cancer have been entered in trials which have matured enough to be clinically meaningful, many uncertainties persist.
Conclusions:
It is now accepted that MAB with steroidal antiandrogens has limited, if any, efficacy. Nonsteroidal antiandrogens appear to be the drugs of choice if MAB is considered. Apart from differences in the nature of the side effects, today there appears to be no major difference between the various types of nonsteroidal antiandrogens (flutamide, nilutamide, bicalutamide). Overall, the impact of MAB on survival and progression-free survival is at best marginal when considering the results of the large meta-analysis published in July 1995. There is undoubtedly a trend in favor of MAB, which hopefully will be confirmed at the next meta-analysis. However, the real target of MAB (patients with minimal disease?) has yet to be defined more accurately as it becomes clear that many patients will not benefit from MAB and should be spared the side effects and cost of antiandrogens. A further point of concern is that continuous administration of any antiandrogen can induce mutations in the androgen receptor, transforming the antiandrogen into an agonist so that the first therapeutic action to be taken in case of progression would be the withdrawal of the antiandrogen. The so-called antiandrogen withdrawal syndrome is, however, less frequent than initially thought.
Insights
Maximal androgen blockade (MAB) using nonsteroidal antiandrogens shows marginal survival benefits for prostate cancer patients. Further research is needed to identify optimal candidates and address potential androgen receptor mutations.
Area of Science:
- Oncology
- Urology
- Pharmacology
Background:
- Maximal androgen blockade (MAB) for prostate cancer treatment remains controversial.
- Despite extensive trials, uncertainties persist regarding MAB's efficacy and optimal use.
- Over 5,000 patients with metastatic prostate cancer have participated in MAB trials.
Purpose of the Study:
- To review the current status of maximal androgen blockade (MAB) in prostate cancer treatment.
- To evaluate the efficacy and modalities of MAB.
- To identify patient subgroups who may benefit from MAB.
Main Methods:
- Review of existing literature and meta-analyses on MAB in prostate cancer.
- Analysis of clinical trial data concerning MAB efficacy and side effects.
- Assessment of antiandrogen mechanisms and potential resistance.
Main Results:
- MAB with steroidal antiandrogens has limited efficacy.
- Nonsteroidal antiandrogens are preferred for MAB, with no significant differences among flutamide, nilutamide, and bicalutamide.
- MAB's impact on survival and progression-free survival is marginal, though a trend favors MAB.
Conclusions:
- MAB efficacy is limited, particularly with steroidal antiandrogens.
- Nonsteroidal antiandrogens are the preferred agents for MAB.
- Further research is needed to define MAB's role and identify responsive patient populations.
- Potential androgen receptor mutations necessitate careful monitoring and consideration of antiandrogen withdrawal.