Clinical trials have utilized intermittent
diethylstilbestrol diphosphate (DES)
therapy in advanced symptomatic prostatic
carcinoma to diminish the morbidity of standard endocrine
therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic
adenocarcinoma 60 days following
tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in
drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in
drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in
drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum
testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum
testosterone returned toward control levels (1.0 ng/ml). Initial mean
tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a
tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in
tumor doubling time was achieved only by rats receiving
castration or high dose DES. Intermittent DES administration controls
tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to
castration.