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Hair Loss Study Abstract: Response of rat and human prostatic cancers to the novel 5 alpha-reductaseinhibitor, SK&F 105657.
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Title
Response of rat and human prostatic cancers to the novel 5 alpha-reductase inhibitor,
SK&F 105657.
Author
Lamb JC; Levy MA; Johnson RK; Isaacs JT
Address
Oncology Center, Johns Hopkins University, School of Medicine, Baltimore, Maryland
21205.
Source
Prostate, 1992, 21:1, 15-34
Abstract
The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R-3327 H
and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5
alpha-reductase inhibitor, SK&F 105657, was tested in vivo. SK&F 105657 was
administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor
and the human PC-82 tumor have a low to undetectable level of tissue 5 alpha-reductase
activity and both responded to SK&F 105657 treatment with a reproducible inhibition of
tumor growth. Associated with this antitumor effect was a major decrease (i.e., greater
than 70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat
R-3327 H prostatic cancer has a much higher level of tissue 5 alpha-reductase activity,
and neither tumor DHT content nor growth of the tumor was inhibited by treatment with
SK&F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar
reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that
produced in R-3327 G tumor-bearing rats which experienced an antitumor response. These
results suggest that SK&F 105657 can produce antitumor effects if a substantial
reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition
of the tissue 5 alpha-reductase enzyme, appears to be more difficult to achieve in tumors
than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue,
prostatic cancers with low 5 alpha-reductase activity could be treated with SK&F
105657 on a dose regimen that lowers serum DHT to surgical castration levels, while
concomitantly inhibiting the already low tumor tissue 5 alpha-reductase activity.
Language of Publication
LA=ENG
Unique Identifier
92350717
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