Chemotherapy

Experimental Chemotherapy

Effect of the 5α-Reductase Inhibitor PNU 156765, Alone or in Combination with Flutamide, in the Dunning R3327 Prostatic Carcinoma Model in Rats

Zaccheo T. · Giudici D. · Panzeri A. · di Salle E.

Author affiliations

Departments of Pharmacology and Chemistry, Oncology Research, Pharmacia & Upjohn, Nerviano, Italy

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Chemotherapy 1998;44:284–292

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Article / Publication Details

First-Page Preview
Abstract of Experimental Chemotherapy

Published online: July 02, 1998
Issue release date: July – August

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

Abstract

The efficacy of treatment with the 5α-reductase inhibitor PNU 156765 (FCE 28260) was investigated in the Dunning R3327 prostatic tumor in rats. The compound, given orally at the doses of 10 and 50 mg/kg/day, for 8 weeks, reduced the growth of established tumors by 49–50%, an effect similar to that of flutamide at 5 mg/kg/day (46% inhibition). In a further experiment, the combination of PNU 156765 10 mg/kg/day and flutamide 5 mg/kg/day resulted in greater inhibition than either treatment alone (70 vs. 20% in PNU-156765-treated and 51% in flutamide-treated groups). The effect of the combination was similar to that of castration (75% inhibition). Ventral prostate weight was more markedly reduced by PNU 156765 than by flutamide, and combined treatment was as effective as castration. Prostatic dihydrotestosterone content was markedly reduced by PNU 156765 while prostatic testosterone increased. Concomitant treatment with flutamide antagonized the testosterone increase induced by PNU 156765. These data indicate a role for 5α-reductase inhibitors in the therapy of prostate cancer, in combination with antiandrogens, in order to achieve adequate androgen blockade with minimal side effects.




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References

  1. Dhom G: Epidemiological aspects of latent and clinically manifest carcinoma of the prostate. J Cancer Res Clin Oncol 1983;106:210–218.
  2. Vogelzang NJ, Kennealey GT: Recent developments in endocrine treatment of prostate cancer. Cancer 1992;70(suppl):966–976.
  3. Bruchovsky N, Rennie PS, Batzold FH, Goldenberg SL, Fletcher T, McLoughlin MG: Kinetic parameters of 5α-reductase activity in stroma and epithelium of normal hyperplastic and carcinomatous human prostates. J Clin Endocrinol Metab 1988;67:806–816.
  4. Brooks JR, Berman C, Nguyen H, Prahalada S, Primka RL, Rasmusson GH, Slater EE: Effect of castration, DES, flutamide, and the 5α-reductase inhibitor, MK-906, on the growth of the Dunning rat prostatic carcinoma, R3327. Prostate 1991;18:215–227.
  5. Zaccheo T, Giudici D, di Salle E: Effect of turosteride, a 5α-reductase inhibitor, on the Dunning R3327 rat prostatic carcinoma. Prostate 1997;30:85–91.
  6. Giudici D, Briatico G, Cominato C, Zaccheo T, Iehlè C, Nesi M, Panzeri A, di Salle E: FCE 28260, a new 5α-reductase inhibitor: In vitro and in vivo effects. J Steroid Biochem Mol Biol 1996;58:299–305.
  7. Geran RI, Greenberg NH, McDonald MM, Schumacher AM, Abbott BJ: Protocol for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 1972;3:1–103.
  8. Schroder FH: 5α-Reductase inhibitors and prostatic disease. Clin Endocrinol 1994;41:139–147.
  9. Andersson S, Russell DW: Structural and biochemical properties of cloned and expressed human and rat steroid 5α-reductases. Proc Natl Acad Sci USA 1990;87:3640–3644.
  10. Bonkhoff H, Stein U, Aumüller G, Remberger K: Differential expression of 5α-reductase isoenzymes in the human prostate and prostatic carcinomas. Prostate 1996;29:261–267.
  11. Silver RI, Wiley EL, Davis DL, Thigpen AE, Russell DW, McConnell JD: Expression and regulation of steroid 5α-reductase 2 in prostate disease. J Urol 1994;152:433–437.
    External Resources
  12. Normington K, Russell DW: Tissue distribution and kinetic characteristics of rat steroid 5α-reductase isozymes: Evidence for distinct physiological functions. J Biol Chem 1992;267:19548–19554.
  13. Brooks JR, Berman C, Primka RL, Reynolds GF, Rasmusson GH: 5α-Reductase inhibitory and anti-androgenic activities of some 4-azasteroids in the rat. Steroids 1986;47:1–19.
    External Resources
  14. Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 1991;354:159–161.
  15. Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS, Darracott Vaughan E, Pappas F, Taylor A, Binkowitz B, Ng J: The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med 1992;327:1185–1191.
  16. Peters DH, Sorkin EM: Finasteride, a review of its potential in the treatment of benign prostatic hyperplasia. Drugs 1993;46:177–208.
  17. Lamb JC, Levy MA, Johnson RK, Isaacs JT: Response of rat and human prostatic cancers to the novel 5α-reductase inhibitor, SKF 105657. Prostate 1992;21:15–34.
  18. Labrie F, Bélanger A, Simard J, Labrie C, Dupont A: Combination therapy for prostate cancer. Cancer 1993;71:1059–1067.
    External Resources
  19. Labrie C, Trudel C, Shengmin L, Martel C, Couet J, Labrie F: Combination of an antiandrogen and a 5α-reductase inhibitor: A further step towards total androgen blockade? Endocrinology 1991;128:566–568.
  20. Fleshner NE, Trachtenberg J: Sequential androgen blockade: A biological study in the inhibition of prostatic growth. J Urol 1992;148:1928–1931.
  21. Chen C, Li X, Singh S, Bélanger A, Labrie F: Additive in vivo growth-inhibitory effects of flutamide and finasteride on androgen-sensitive Shionogi 115 carcinoma. Endocr Relat Cancer 1996;3:217–227.
  22. Fleschner NE, Fair WR: Anti-androgenic effects of combination finasteride plus flutamide in patients with prostatic carcinoma. Br J Urol 1996;78:907–910.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Experimental Chemotherapy

Published online: July 02, 1998
Issue release date: July – August

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE


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