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928P LHRH AGONIST-INDUCED SUPPRESSION OF THE
ANDROGEN SYNTHESIS PATHWAY IN PROSTATE CANCER
J. Pinski, S. Xiong, Q. Wang, S.V. Liu
Division of Medical Oncology, University of Southern California Norris
Comprehensive Cancer Center, Los Angeles, CA, UNITED STATES OF
AMERICA
Background: Standard first-line therapy for advanced prostate cancer (PC) includes
the use of a luteinizing hormone releasing hormone (LHRH) agonist. While the
primary site of action for these agents is the pituitary-hypothalamic-gonadal axis,
receptors fo LHRH are also present in the membrane of PC cells and mediate a
direct anti-tumor effect. The mechanism of this effect has been largely unexplored
and may harbor a context of vulnerability. Previously, we have demonstrated that
luteinizing hormone (LH) increases de novo steroidogenesis in PC cells and silencing
of the LH receptor leads to downregulation of steroidogenesis. Here, we examined
the impact of LHRH agonists on this process at the cellular level.
Methods: LNCaP PC cells were treated with the LHRH agonist buserelin for 8 hours
in the presence or absence of the LHRH antagonist antide. Gene expression of LH
and androgen synthesis enzymes was quantified by real-time polymerase chain
reaction and protein expression was measured with Western blot. Cell proliferation
was assessed in these cells using MTS assays.
Results: The LHRH agonist buserelin significantly suppressed the gene expression of
LH and the androgen synthesis enzymes AKR1C1, AKR1C2, AKR1C3, CYP11A1
and RDH5 (p < 0.05). Protein expression of LH, AKR1C1, AKR1C3 and CYP17A1
was also inhibited by buserelin treatment (p < 0.05). Buserelin also suppressed
LNCaP cell proliferation in a dose-dependent manner (p < 0.05). The suppressive
effects of buserelin on gene expression, protein expression and cell proliferation were
mitigated by the LHRH antagonist antide.
Conclusion: These data implicate the LHRH agonist buserelin in the direct inhibition
of de novo tumoral steroidogenesis, which may be mediated by suppression of LH.
The LH pathway warrants further investigation as a therapeutic target.
Disclosure: All authors have declared no conflicts of interest.
929P LOW-DOSE DETHYLSTILBESTROL IN
CASTRATION-RESISTANT PROSTATE CANCER
A. Sasse 1 , C.L. Nourani 2 , L.O. Reis 3
1 Cevon Centre For Evidences In Oncology, UNICAMP - Universidade Estadual
de Campinas, Campinas, BRAZIL, 2 Oncology, UNICAMP, Campinas, BRAZIL,
3 Urology, UNICAMP, Campinas, BRAZIL
Introduction: The role of sequential lines of hormone therapy in castration-resistant
prostate cancer (CRPC) remains unclear. Currently, the standard treatment for
patients with CRPC is chemotherapy. Diethylstilbestrol (DES) is a synthetic estrogen
with anti-tumour properties, which could be effective in these patients, before
chemotherapy. OBJECTIVE: To determine the efficacy and safety of low-dose DES in
second-line hormonal therapy for CRPC patients in a single institution.
Methods: Between 2007 and 2012, a total of 31 patients with metastatic CRPC
received DES 1 mg daily. All patients had progression after central androgenic
suppression and at least one line of androgen antagonists (bicalutamide and/or
flutamide). Central androgenic supression with bilateral orchiectomy or a
gonadotropin-releasing hormone agonist was maintained. Aspirin 100 mg daily was
administered to all patients to minimize risk of thromboembolism. The data of PSA
response (defined as a 50% reduction), progression-free survival (PFS), overall
survival and adverse events were collected and analyzed.
Results: The median age was 76,8 years. The PSA response rate was 55%. After a
median follow up of 22 months, the median PFS was 12 months. Only one patient
died at the time. The main adverse event was gynecomastia (11/31, 35.4%) and no
thrombotic event was recorded.
Conclusion: Low-dose DES appears to be safe and effective for metastatic CRPC
before initiating chemotherapy.
Disclosure: All authors have declared no conflicts of interest.
930P WHAT PATIENT GROUPS HAVE SPECIAL BENEFITS USING
THE GNRH-ANTAGONIST DEGARELIX? CONCLUSIONS
BASED ON REAL LIFE DATA FROM A GERMAN REGISTRY
G. Geiges 1 , M. Schulze 1 , M. Gedamke 2
1 Uro-oncology, IQUO, Berlin, GERMANY, 2 Urology/Uro-Oncology, Ferring
Arzneimittel GmbH, Kiel, GERMANY
Introduction and objective: The GnRH-antagonists, especially degarelix, are still
relatively new substances in the treatment of prostate cancer. Data on advantages of
this specific approach to ADT is accumulating. It is of interest to understand which
patient groups have a special benefit in using degarelix. We have collected data on
efficacy and safety of degarelix in daily practice in order to compare with data from
clinical studies.
Annals of Oncology
Methods: Data from 421 patients with prostate cancer treated with degarelix were
collected by 93 office based urologists. Previous treatment, concomitant medication,
tumour stage and grade as well as alkaline phosphatase (ALP), prostate volume,
testosterone, PSA and side-effects were documented over a period of up to 2 years or
until completion of therapy.
Results: Tumour stages were documented at baseline as T1 27.9%, T2 22.0%, T3
25.1%, T4 13.1% and Tx 11.5%. Median PSA at baseline was 12.4 ng/mL.
Testosterone was above castration level (>0.5 ng/mL) in 41.7% of patients (pts) with
previous hormone therapy and available testosterone value at inclusion (n = 48). In
14.5% of the pts degarelix was used intermittently. Prostate volume measured by
transrectal ultrasound was reduced by 40.8% within 3 months compared to baseline.
For pts in which ALP was measured (n = 61), ALP was suppressed from a median of
639.9 (IU/L) to 108.7 (IU/L) after 2 months and was still suppressed to 78.6 (IU/L)
at month 12. Treatment of pts with prior hormone-therapy resulted in 53.8% in a
stable PSA after 1 year. PSA-reduction to