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Titolo:
Rationale for combination ketoconazole/vitamin D treatment of prostate cancer
Autore:
Peehl, DM; Seto, E; Feldman, D;
Indirizzi:
Stanford Univ, Sch Med, Dept Urol, Stanford, CA USA Stanford Univ Stanford CA USA Univ, Sch Med, Dept Urol, Stanford, CA USA Stanford Univ, Sch Med, Dept Med, Stanford, CA USA Stanford Univ StanfordCA USA Univ, Sch Med, Dept Med, Stanford, CA USA
Titolo Testata:
UROLOGY
fascicolo: 2A, volume: 58, anno: 2001, supplemento:, S
pagine: 123 - 126
SICI:
0090-4295(200108)58:2A<123:RFCKDT>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
VITAMIN-D DEFICIENCY; CELL-LINES; ORCHIECTOMY; CALCITRIOL; EFFICACY; RISK; D-3;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Peehl, DM Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 rol, Stanford, CA 94305 USA
Citazione:
D.M. Peehl et al., "Rationale for combination ketoconazole/vitamin D treatment of prostate cancer", UROLOGY, 58(2A), 2001, pp. 123-126

Abstract

The high rate of progression of prostate cancer after androgen deprivationtherapy mandates that new strategies be developed. Adjuvant therapy combined with androgen deprivation may slow or prevent progression. Ketoconazole plus calcitriol therapy is an example of I such a combination with a mechanistic basis for synergistic activity. Ketoconazole is commonly used as a second-line androgen deprivation therapy. This imidazole derivative is an inhibitor of P-450 enzymes, including those involved in steroidogenesis. OtherP-450 enzymes that are inhibited by ketoconazole include 1 alpha -hydroxylase and 24-hydroxylase, which metabolize vitamin D. Growth inhibition of prostate cancer cells by vitamin D depends on levels of the active metabolite, 1,25-dihydroxyvitamin D-3 (calcitriol). The enzyme 24-hydroxylase converts calcitriol to less active products. The inhibition of 24-hydroxylase by ketoconazole maintains the magnitude and duration of response to calcitriol. Combined ketoconazole/calcitriol therapy might therefore potentiate the antitumor activity of calcitriol. Because androgen-independent prostate cancer cells often remain responsive to growth inhibition by calcitriol, it is also possible that calcitriol would slow or prevent development of androgen-independent cancer growth. Another consideration is that ketoconazole blocks 1 a-hydroxylase activity, which is the key enzyme that creates calcitriolin the body. Therefore, patients receiving ketoconazole therapy are likelyto be deficient in vitamin D. The detrimental consequences of vitamin D deficiency in these patients would also be alleviated by the addition of calcitriol to the therapeutic regimen. (C) 2001, Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 01:44:31