Androgen stimulated chemotherapy in the dunning R-3327 prostatic adenocarcinoma

Abstract

This study was undertaken to determine whether hormonal stimulation followed by chemotherapy with a cell-cycle specific agent would improve the effectiveness of the chemotherapy in a prostatic adenocarcinoma model. One hundred Copenhagen rats were randomised into 5 equal groups and injected subcutaneously with 2 x 10(7) cells of Dunning G strain prostatic adenocarcinoma. The groups were treated in the following fashion: 1. sham operated controls, 2. castration, 3. castration and methotrexate, 4. castration, testosterone and methotrexate and 5. castration and testosterone. When the tumours became palpable, all animals received the surgery to which they were randomised. Subsequent hormonal and chemotherapy was started 1 week thereafter. Therapy was given for 5 consecutive days followed by a 16-day recovery period and then continued in a cyclical fashion. Serial measurements of animal weights and tumour size were obtained. Analysis of tumour growth was restricted to the first 29 days of therapy because of a rapid decline in animal survival beyond that point. The group treated with castration, testosterone, and methotrexate inhibited tumour growth more than any other group and was the only group that was significantly different from control (P less than 0.05).

Modalities of chemotherapy and endocrine therapy for growth inhibition of androgen‐stimulated mouse carcinoma (shionogi carcinoma 115)

“…Treatment with a submaximal level of testosterone, but not with the maximal level, enhances the effect of chemotherapy in the SC 115 after castration, which may be accounted for by acceleration of the cell cycle [ 171. A similar effect of testosterone on the effectiveness of chemotherapy was reported in the R 3327-G rat prostatic tumor grown in the castrated animals [18] and in advanced prostatic cancer refractory to orchiectomy [ 19,201. Although influences of androgen on the effect of chemotherapy in these reports seem to be contrary to those in the present study, experimental conditions are clearly different; in these reports testosterone and cytotoxic drug are injected simultaneously while in the present study an enhanced effect of the cytotoxic drug is obtained in tumor relapsing under unfavorable conditions induced by androgen deprivation.…”

The Importance of Continued Endocrine Treatment during Chemotherapy of Hormone- Refractory Prostate Cancer

“…The patients de scribed here show that the situation where the androgenindependent cells are sensitive to chemotherapy and the androgen-sensitive cells are resistant to it occurs not uncommonly. An opposite point of view is that endocrine stimulation of tumour growth is likely to enhance the response to chemotherapy [8], a hypothesis which our observations seem to disprove because re-starting hor mone therapy is critical to the continued response to che motherapy.…”

“…The en hanced tumour growth due to re-exposure to androgens seen in our patients may be explained if there were two populations of tumour cells, one which is androgen-inde pendent and another androgen-sensitive. Where chemo therapy is neither effective against the androgen-sensitive Androgen Deprivation during Chemotherapy for Prostate Cancer Eur Urol 1997;31: [7][8][9][10] vantage for continued androgen deprivation in hormonerefractory disease. However, our results suggest that, in a proportion of patients at least, continuation of previously effective endocrine therapy is necessary to observe a response to chemotherapy.…”