Download CASTRATION-RESISTANT PROSTATE CANCER (CRPC

CASTRATION-RESISTANT PROSTATE CANCER (CRPC):
COMBINATION THERAPY OF ETHINYLESTRADIOL AND
ESTRAMUSTINE PHOSPHATE REINTRODUCES OBJECTIVE CLINICAL
RESPONSES.
E. De Berardinis, G.M. Busetto, S. Salciccia, F. Di Silverio and V. Gentile.
Sapienza Rome University Policlinico Umberto I.
Scopo del lavoro
Therapy for castrate-resistant prostate cancer (CRPC) centers on suppressing systemic
androgens and blocking activation of the androgen receptor (AR). Despite anorchid serum
androgen levels, nearly all patients develop castration-resistant disease. At this stage of
the disease treatment is generally based on chemotherapy. In our research we wanted to
evaluate whether a combination therapy of ethinylestradiol and estramustine phosphate
was able to reintroduce an objective clinical response in these patients with refractory
prostate cancer.
Materiali e Metodi
31 patients (11 pts. Gleason score 8 (4+4), 13 pts. Gleason score 9 (5+4), 5 pts. Gleason
score 10 (5+5)) with stage D3 disease and bone metastases who had progression despite
initial responses to combined androgen blockade and in whom antiandrogen withdrawal
subsequently failed discontinued combined androgen blockade and received 2 mg
ethinylestradiol orally daily and oral estramustine 420 mg/daily. Serum prostate specific
antigen (PSA), Eastern Cooperative Oncology Group performance status and bone pain
scores were assessed at regular intervals. Median followup was 17 months (range 8 to
26).
Risultati
All cases (90%, 95% CI 55.5 to 99.8) had an objective clinical response, defined as a
greater than 50% PSA decrease (median 87.1%, range 50.2% to 94.4%). PSA
normalization (less than 4 ng/ml) was achieved in 3 cases. All patients reported significant
and durable improvement in bone pain (median duration 17.5 months) and performance
status (median duration 18 months). The most important side effects were: vein
thrombosis (8 pz) and gastric pain (5 pz).
Discussione
Recent studies have shown that prostatic carcinoma cell becomes sensitive to low levels
of androgens and that they themselves are produced by prostate cancer cells, or derived
from the adrenal.
Next to this interesting basic research, there is confirmation that prostate cell has an
increased number of beta estrogen receptors (quantity) in addition to their overexpression
(quality).
Conclusion
Is by now proven that CRPC is sensitive to androgens and prostate cancer could become
hypersensitive to androgens low levels and is finally established that this cancer produces
androgens by itself.
We could improve our results in term of DFS and related therapy side-effects substituting
Estracyt with new antiandrogen
maintaining ethinylestradiol that acts on beta-oestrogenic receptors.
References
1) Di Silverio F, Gagliardi V, Sorcini G, Sciarra F. Biosynthesis and methabolism of
androgenic hormones in cancer of the prostate. Invest Urol 1976;13(4):286-8.
2) Montgomery RB, Mostaghel EA, Vessella R, et al. Maintenance of intratumoral
androgens in metastatic prostate cancer: a mechanism for castration-resistant
tumor growth. Cancer Res 2008;68:4447–54.
3) Yap TA, Carden CP, Attard G, de Bono JS. Targeting CYP17: established and
novel approaches in prostate cancer. Curr Opin Pharmacol 2008;8:449–57.
4) Tindall DJ, Rittmaster RS. The rationale for inhibiting 5α-reductase isoenzymes
in the prevention and treatment of prostate cancer. J Urol 2008;179:1235–42.