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Article

Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience

  • Authors:
    • Tal Grenader
    • Yevgeni Plotkin
    • Maya Gips
    • Nathan Cherny
    • Alberto Gabizon
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Shaare Zedek Medical Center, and Hebrew University-School of Medicine, Jerusalem, Israel
  • Pages: 428-434
    |
    Published online on: November 14, 2013
       https://doi.org/10.3892/or.2013.2852
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Abstract

The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Forty-three DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.
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1 

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, et al: Cancer treatment and survivorship statistics. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar

2 

Huang X, Chau CH and Figg WD: Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures. J Hematol Oncol. 5:352012. View Article : Google Scholar

3 

Wilkins A, Shahidi M, Parker C, Gunapala R, Thomas K, Huddart R, Horwich A, et al: Diethylstilbestrol in castration-resistant prostate cancer. BJU Int. 110:E727–E735. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci M, et al: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 26:1148–1159. 2008. View Article : Google Scholar

5 

Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, Burch PA, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. New Engl J Med. 351:1513–1520. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Tannock IF, De Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New Engl J Med. 351:1502–1512. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, Ettinger SL, Gleave ME and Nelson CC: Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 68:6407–6415. 2008.PubMed/NCBI

8 

Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD and Nelson PS: Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 68:4447–4454. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Aggarwal R, Weinberg V, Small EJ, Oh W, Rushakoff R and Ryan CJ: The mechanism of action of estrogen in castration-resistant prostate cancer: clues from hormone levels. Clin Genitourin Cancer. 7:E71–E76. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Huggis C and Hodges CV: Studies on prostatic cancer. I The effects of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1:293–297. 1941.

11 

Veterans Administration Cooperative Urological Research Group. Carcinoma of the prostate: treatment comparison. J Urol. 98:516–522. 1967.

12 

Bosset PO, Albiges L, Seisen T, De la Motte Rouge T, Phé V, Bitker MO and Rouprêt M: Current role of diethylstilbestrol in the management of advanced prostate cancer. BJU Int. 110:E826–E829. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Malkowicz SB: The role of diethylstilbestrol in the treatment of prostate cancer. Urology. 58:108–113. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Kitahara S, Yoshida K, Ishizaka K, Kageyama Y, Kawakami S, Tsujii T and Oshima H: Stronger suppression of serum testosterone and FSH levels by a synthetic estrogen than by castration or an LH-RH agonist. Endocr J. 44:527–532. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Robinson MR, Smith PH, Richards B, Newling DW, De Pauw M and Sylvester R: The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol. 28:273–283. 1985.

16 

Montgomery B, Nelson PS, Vessella R, Kalhorn T, Hess D and Corey E: Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer. BMC Cancer. 10:2442010. View Article : Google Scholar : PubMed/NCBI

17 

Rosenbaum E, Wygoda M, Gips M, Hubert A, Tochner Z and Gabizon A: Diethylstilbestrol is an active agent in prostatic cancer patients after failure to complete androgen blockade. Proc J Clin Oncol. 19:349a2000.

18 

Clemons J, Glodé LM, Gao D and Flaig TW: Low-dose diethylstilbestrol for the treatment of advanced prostate cancer. Urol Oncol. 31:198–204. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Shamash J, Stebbing J, Sweeney C, Sonpavde G, Harland S, Dawkins G, Brock C, et al: A validated prognostic index predicting response to dexamethasone and diethylstilbestrol in castrate-resistant prostate cancer. Cancer. 116:3595–3602. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Manikandan R, Srirangam SJ, Pearson E, Brown SC, O’Reilly P and Collins GN: Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial. Urol Int. 75:217–221. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Orlando M, Chacón M, Salum G and Chacón DR: Low-dose continuous oral fosfestrol is highly active in ‘hormone-refractory’ prostate cancer. Ann Oncol. 11:177–181. 2000.PubMed/NCBI

22 

Smith DC, Redman BG, Flaherty LE, Li L, Strawderman M and Pienta KJ: A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer. Urology. 52:257–260. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Robertson CN, Roberson KM, Padilla GM, O’Brien ET, Cook JM, Kim CS and Fine RL: Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst. 88:908–917. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Hartley-Asp B, Deinum J and Wallin M: Diethylstilbestrol induces metaphase arrest and inhibits microtubule assembly. Mutat Res. 143:231–235. 1985. View Article : Google Scholar : PubMed/NCBI

25 

Geier R, Adler S, Rashid G and Klein A: The synthetic estrogen diethylstilbestrol (DES) inhibits the telomerase activity and gene expression of prostate cancer cells. Prostate. 70:1307–1312. 2010.PubMed/NCBI

26 

Ho SM: Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. J Cell Biochem. 91:491–503. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Schulz P, Link TA, Chaudhuri L and Fittler F: Role of the mitochondrial bc1-complex in the cytotoxic action of diethylstilbestrol-diphosphate toward prostatic carcinoma cells. Cancer Res. 50:5008–5012. 1990.PubMed/NCBI

28 

de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, et al: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 376:1147–1154. 2010.

29 

Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW and Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med. 363:411–422. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Gerger A, Langsenlehner U, Kapp K and Langsenlehner T: Overall survival benefit and safety profile of radium-223 chloride, a first-in-class alpha-pharmaceutical: results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases. J Clin Oncol. 30(Suppl 5): 82012.

31 

Kmietowicz Z: NICE recommends abiraterone for prostate cancer after manufacturer reduces price. BMJ. 344:e35202012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Grenader T, Plotkin Y, Gips M, Cherny N and Gabizon A: Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience. Oncol Rep 31: 428-434, 2014.
APA
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., & Gabizon, A. (2014). Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience. Oncology Reports, 31, 428-434. https://doi.org/10.3892/or.2013.2852
MLA
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., Gabizon, A."Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience". Oncology Reports 31.1 (2014): 428-434.
Chicago
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., Gabizon, A."Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience". Oncology Reports 31, no. 1 (2014): 428-434. https://doi.org/10.3892/or.2013.2852
Copy and paste a formatted citation
x
Spandidos Publications style
Grenader T, Plotkin Y, Gips M, Cherny N and Gabizon A: Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience. Oncol Rep 31: 428-434, 2014.
APA
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., & Gabizon, A. (2014). Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience. Oncology Reports, 31, 428-434. https://doi.org/10.3892/or.2013.2852
MLA
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., Gabizon, A."Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience". Oncology Reports 31.1 (2014): 428-434.
Chicago
Grenader, T., Plotkin, Y., Gips, M., Cherny, N., Gabizon, A."Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience". Oncology Reports 31, no. 1 (2014): 428-434. https://doi.org/10.3892/or.2013.2852
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