Early results from our group have shown the selenium compound, MSC, potentiates the antitumor activity of a wide range of cancer chemotherapeutic drugs against human colon and head & neck tumor xenografts. The present study was designed to test if MSC can increase the antitumor activity of Taxotere against prostate cancer using the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. Taxotere was administered by a single i.v. injection at 40 and 80 mg/kg. The maximum tolerated dose (MTD) was 80 mg/kg i.v. x 1. MSC was administered p.o 0.2 mg/mouse/day daily for 14 days with the first dose starting 7 days prior to Taxotere treatment and continued 7 days post Taxotere treatment for a total of 14 days. All mice had palpatable tumor at the start of treatment. The effects of Taxotere alone and in combination with MSC were evaluated 10 days post Taxotere treatment by urogenital weight and prostate weight. Tumor incidence was 90% in the Control group (9/10), 80% in Taxotere 40 (8/10), 50% in MSC & Taxotere 40 (5/10), 78% in Taxotere 80 (7/9) and 14% in MSC & Taxotere 80 (1/7). Thus MSC in combination with Taxotere substantially reduced the tumor incidence. UG weights were decreased in the treatment groups receiving MSC & Taxotere (40 & 80 mg/kg) compared to control (P<.05). There was a trend towards decreased UG weight in MSC & Taxotere compared to Taxotere alone (P<.08). There was no difference in UG weight between control and Taxotere alone. Prostatic weight was decreased in the MSC & Taxotere 80 group compared to control (P<.05). A similar trend was observed in the MSC & Taxotere 40 group (P=.06). In the groups treated with Taxotere alone (40 or 80) there was a trend towards decrease prostatic weight compared to control. There was no difference in prostatic weight between Taxotere alone and Taxotere in combination with MSC. A small subset of animals was also analyzed by MRI with similar results. In conclusion MSC seems to potentiate and modulate the efficacy of Taxotere in androgen dependent prostate cancer in the TRAMP model as indicated by a reduction on UG weight and decreased incidence of tumors. These findings may have a direct clinical impact on future protocols using Taxotere in combination with MSC for prostate cancer.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]