| Ch 10 | Page 5/ 14 | |
| Cancer hormonotherapy |
Steroid hormones | |
Androgens were previously used for treating metastatic breast carcinoma.
They induce a castration effect by blocking hypothalamus hormones.
The virilisation observed in long_term treatment, together with the risks of hypertension and the appearance of new drugs, far better tolerated by patients, have led to the disappearance of androgens from the therapeutical repertoire, except (perhaps) in pre-terminal phases when their anabolising effect can be useful (improved appetite, lesser asthenia).
Oestrogens were, for a long time, used to treat prostate cancer.
The most frequently used drugs were diethylstilbestrol as well as estradiol di-undecylate (or Oestradiol –Depot ).
They have peripheral side effects which are symptoms of feminisation: gynaecomastia, altered repartition of fatty tissue), however their main action consists in blocking the secretion of the hypothalamus hormone LH RH, thus inducing a suppression of LH by the pituitary gland and secondarily of testosterone by the testis.
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Mechanisms of action of oestrogens for prostate cancer |
Chemical castration is therefore obtained without hot flushes.
Oestrogens (especially at high prolonged dosages 3mg/d) have been abandoned because of the thrombosis and embolism complications that they induce and which diminish the positive effect of the treatment in randomised studies. Unfortunately, a dosage of 1 mg/d may not be sufficient for all patients. Thus, (at least in France), oestrogens are no longer a first-line hormonal treatment for prostate cancer.
Following the failure of first-line hormonal treatment, DES may offer significant responses.
Oestrogens can also be used in a loading dose (for acute complications which are not amenable to surgery or radiotherapy, such as diffuse medullar compression or very intense pain).
Fosfetrol (or ST 52) is a prodrug which brings the active agent to the prostate. Dephosphorylation induces the formation of the active metabolite: diethylstilbestrol (DES). Due to the presence of acid phosphatases, Fosfetrol is mainly (but not solely) transformed at the tumour site, which avoids general oestrogen treatment and a much higher dosage to the prostate, thus limiting the risk of gynaecomastia, thrombosis and pulmonary embolism.
Moreover, as for oestrogens, the inhibition of the hypothalamus-pituitary axis is observed, thus reducing the testicular synthesis of androgens.
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