Andrew V. Schally

An oriented phase-II trial of D-Trp6-LH-RH in patients with prostatic carcinoma

An oriented phase II trial ofD-Trp6-LH-RH was conducted according to Gehans statistical method on 25 patients suffering from prostatic carcinoma.LH and testosterone serum levels decreased rapidly. Pain disappeared during the third month in 14 out of the 21 patients and markedly decreased in 5. Prostatism completely regressed in 10 out of the 22 subjects presenting it and markedly decreased in 9. Prostate hypertrophy regressed as shown by ultrasonography, in 84% and by more than 50% in 37% of the patients. The overall regression rate of bone scintigraphy images was 43%; a regression of more than 50% was only registered in 12.5% of the patients; this may be explained by the long time which is necessary before bone image disappearance occurs. Prostatic acid phosphatase levels regressed in 75% and by more than 50% in 66.7% of the patients.

Inhibition of the growth of some hormone dependent tumors by D-Trp6-LH-RH.

We have investigated the effects of chronic administration of D-Trp6-LH-RH on the growth of various hormone dependent tumors in rats and mice. Treatment of male Copenhagen F-1 rats bearing the Dunning R-3327 H prostate adenocarcinoma with 25 μg of D-Trp6-LH-RH bid for 21 days significantly reduced tumor weight and volume as compared to controls. Serum LH, prolactin and testosterone levels in Copenhangen F-1 rats bearing Dunning tumors were significantly decreased after treatment with D-Trp6-LH-RH. Administration of D-Trp6-LH-RH in does of 25 μg/day for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. In rats bearing the MT/W9A mammary adenocarcinoma, D-Trp6-LH-RH, at a dose of 25 μg bid for 28 days significantly decreased tumor weight and volume. Administration of D-Trp6-LH-RH in a dose of 25 μg/day, 3–18 days after inoculation with the tumor, inhibited the growth of the prolactin (PRL) and ACTH-secreting pituitary tumor 7315a in female Buffalo rats. In three experiments D-Trp6-LH-RH (30–60 μg/day) decreased tumor weight and/or volume of the Swarm chondrosarcoma. Regression of these hormone-dependent tumors in rats and mice in response to chronic administration of D-Trp6-LH-RH suggests that this compound can be used for treatment of prostate cancer and breast cancer, and also considered for the development of a new endocrine therapy for chondrosarcomas, osteosarcomas, pituitary tumors and other hormone-dependent neoplasias. The demonstration of the successful use of LH-RH agonsits for the palliative management of stage C and D prostate cancer has already shown that this treatment could be employed instead of surgical orchiectomy or estrogen therapy. Preliminary clinical trials suggest that agonists of LH-RH might also be of help in the treatment of breast cancer in premenopausal women.