ESTRAMUSTINE POTENTIATES THE RADIATION EFFECT IN HUMAN PROSTATE TUMOR-TRANSPLANT IN NUDE-MICE

In this study, we have investigated the combined effect of estramustin e treatment and external beam radiation on human prostatic cancer tumo r cells (DU 145) transplanted in nude mice. The treatment was given ac cording to two different schedules. In the first treatment regimen, es tramustine was administered intraperitoneally (i.p.) intermittently fo r 20 days. The radiation therapy, which was started on day 9, was give n with 6 Gy fractions during an 11-day-long period to a total dose of 36 Gy. The combination treatment (estramustine + radiation) resulted i n a significant tumor growth retardation as compared to the control gr oup. This pronounced effect was seen neither with radiation alone nor with estramustine alone. In order to further extend the radiation trea tment time, a second therapy regimen was employed. In this part of the study, estramustine was administrated i.p. intermittently for 26 days . The radiation therapy, which was started on day 6, was given with 4 Gy fractions during a 21-day-long period to a total dose of 40 Gy. Und er these conditions, a significant tumor growth retardation was disclo sed, when comparing the combination treatment (estramustine + radiatio n) with radiation alone. The tumors were analyzed for content of necro sis and proliferative activity. The largest proportion of necrosis was seen in the combination (estramustine+ radiation) treatment group. Al so, the tumors from this group expressed a decreased proliferative act ivity. The data indicate that estramustine acts as a radiosensitizing agent in human prostatic cancer cells in vivo. The radiosensitizing pr operties of the drug encourage further studies with respect to clinica l application. (C) 1994 Wiley-Liss, Inc.