Literature DB >> 14743469

Anti-tumor effect of combination therapy with intratumoral controlled-release paclitaxel (PACLIMER microspheres) and radiation.

Rena G Lapidus1, Wenbin Dang, David Marc Rosen, Alyssa M Gady, Yelena Zabelinka, Robert O'Meally, Theodore L DeWeese, Samuel R Denmeade.   

Abstract

BACKGROUND: Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism.
METHODS: Orthotopic LNCaP tumors were injected with 40% PACLIMER Microspheres (40% loading; w:w) when tumors were 100-200 mm(3). Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm(3). Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time.
RESULTS: Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P < 0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres.
CONCLUSIONS: A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers. Copyright 2003 Wiley-Liss, Inc.

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Year:  2004        PMID: 14743469     DOI: 10.1002/pros.10331

Source DB:  PubMed          Journal:  Prostate        ISSN: 0270-4137            Impact factor:   4.104


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