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Prostate disease and the pharmaceutical industry
Prostate Cancer
Medicines for more advanced disease
Much can now be done for men diagnosed with prostate cancer:
surgery, external or internal radiotherapy, or hormone medicines
can extend life by many years and, at best, for two or more
decades. Despite this, prostate cancer still kills around
10,000 men in the UK every year.
There are two main reasons for this high death toll. Firstly,
many men are diagnosed too late for their cancer to be cured.
Secondly, the response obtained with hormone medicines does
not last indefinitely and after a few years of treatment,
the cancer may become resistant.
Resistance appears because the original tumour contains a
mixture of hormone-responsive, hormone-dependent, and hormone-independent
cells which respond differently to medicines. Early in the
disease, most cells in the tumour will be responsive and will
die. Those that are dependent on testosterone or DHT will
cease to grow as the natural hormones are blocked. A small
number of independent cells has an inbuilt ability to grow
without natural hormone stimulation. Hence, as the treatment
takes effect, this last group gradually takes over and control
is lost. This is called ‘hormone escape’ and calls for different
medical treatment.
Once hormone escape has occurred, the doctor may adopt second-line
treatments. There are several cancer medicines that can be
used in hormone-resistant prostate cancer both alone and in
various combinations. They include cyclophosphamide (Asta
Medica), 5-fluorouracil (Schering Health Care, Cambridge Laboratories),
vincristine (Eli Lilly), cisplatin and epirubicin (Pharmacia).
Partial responses are usual with these agents, with improvements
in the quality of life and pain score. However, most display
side effects that detract from their value, and survival at
this stage is often less than a year.
Two compounds that continue to attract clinical interest
are estramustine phosphate (Pharmacia, Pierre Fabre) and the
vinca alkaloid, vinorelbine (Pierre Fabre). These have been
assessed alone and in various combinations and have displayed
activity in some people, with manageable toxicity. Preliminary
trials have also been conducted with paclitaxel (Bristol-Myers
Squibb) in hormone-resistant prostate cancer with claims of
benefit. This medicine is available in the UK for ovarian,
breast and some lung cancers, but its use in prostate cancer
is still only experimental. This is also true of the related
compound, taxotere (Aventis), also available for breast and
lung cancer, which is now in Phase 3 trials. There is a great
need for more effective medicines specifically targeted on
advanced hormone-resistant prostate cancer.
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