Intratumoral delivery of paclitaxel for treatment of orthotopic prostate cancer.

Locally recurrent prostate cancer can lead to significant morbidity, metastasis, and even death. The objective of this study was to evaluate the efficacy of an injectable polymeric paste formulation containing paclitaxel against orthotopic prostate tumor in rats. The Dunning R-3327 rat prostate adenocarcinoma is experimental tumor model used to study tumor progression. The polymer loaded with paclitaxel was injected into the tumor bearing prostate glands of the rats 3 days after tumor cell inoculation. In control untreated rats, tumor volume reached 14 cm(3) after 25 days, while in rats treated with intratumoral injection of polymer/paclitaxel formulation the prostate volume with the tumor was only 0.9 cm(3), 35 days posttumor cells inoculation. In the group treated with intratumoral injection of paclitaxel suspension, the tumor volume was 6.6 cm(3), and in the group treated with intraperitonial (IP) paclitaxel formulation, the tumor volume reached 13.9 cm(3) 25 days posttumor cells inoculation. No metastases were found in rats treated intratumorally with 200 microL of polymer/paclitaxel formulation, while rats in other treatment groups developed metastases in the lungs and lymph nodes. The results of this study indicated that a site-directed, injectable, controlled release formulation of paclitaxel is effective against localized prostate tumors and metastasis. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association