1994 Fiscal Year Final Research Report Summary
Investigation of combined antiandrogens with LH-RH analogue for prostate cancer
| Project/Area Number |
05671301
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | University of Tokyo |
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Principal Investigator |
HOMMA Yukio University of Tokyo(Hospital), Department of Urology, Lecturer, 医学部(病), 講師 (40165626)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMATSU Hiroaki University of Tokyo(Hospital), Department of Urology, Assistant, 医学部・附属病院, 助手 (60251295)
FUKAZAWA Ritsu University of Tokyo(Hospital), Department of Urology, Assistant, 医学部・附属病院, 助手 (90251305)
TAKAI Kazuhiro University of Tokyo(Hospital), Department of Urology, Assistant, 医学部・附属病院, 助手 (80154730)
TANAKA Yoshinori University of Tokyo(Hospital), Department of Urology, Assistant, 医学部・附属病院, 助手 (50236650)
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| Project Period (FY) |
1993 – 1994
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| Keywords | prostate cancer / endocrine therapy / LH-RH analogue / flare up phenomenon / antiandrogen / testosterone |
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| Research Abstract |
Lutenizing hormone-releasing hormone analogue (LH-RH) is useful alternative for castration in the treatment of prostate cancer. A initial injection of LH-RH causes transient increase of serum testosterone (T surge), which may cause progression of the disease, so called "flare up phenomenon". Our preliminary study in 1993 on combined treatment of antiandrogens with LH-RH had shown no inhibitory effect in T surge. This was probably because of small dosage and weak negative feed back to hypothalamus pituitary system of antiandrogens. In 1994, to determine adequate time and dosage of antiandrogens for preventing "flare up", increased doses of two steroidal compound, chlormadinone acetate, 17-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238) and a non-steroidal one, flutamide (FL) were investigated in 15 week-old Wistar rats. Antiandrogens were given by gavage for 0 or 7 days before injection of 1mg/kg of LH-RH subcutaneously. Serum T was measured after 2 hours of LH-RH injection and prostate was resected for PCNA staining after 3 days. As results, 1)A single injection of LH-RH increased serum T,prostate weight and labeling index (L.I.) of PCNA.2)Steroidal antiandrogens showed no inhibition of T surge and weak suppression of prostate cell growth. 3)Non-steroidal antiandrogen didn't inhibit T surge, which intensified it in the longer duration and the larger dosage. But FL achieved significant suppression of the cell growth. Although these results can't establish proper regimen for prevention of T surge, it is suggested that foregoing steroidal antiandrogens should be followed with simultaneous administration of non-steroidal one at LH-RH injection.
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Research Products
(1 results)
