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Clinical

A polymeric paste-drug formulation for intratumoral treatment of prostate cancer

Prostate Cancer and Prostatic Diseases volume 23, pages 324–332 (2020)Cite this article

Subjects

Abstract

Objective

Focal therapy has emerged as a treatment option for low- to intermediate-risk localized prostate cancer (PCa) patients, to balance the risks for urinary and sexual morbidity of radical treatment with the psychological burden of active surveillance. In this context, we developed ST-4PC, an injectable, polymeric paste formulation containing docetaxel (dtx) and bicalutamide (bic) for image-guided focal therapy of PCa. The objective of this work was to evaluate the in vitro characteristics and in vivo toxicity and efficacy of ST-4PC.

Material and methods

In vitro drug release was evaluated using high-performance liquid chromatography. In vivo toxicity of blank- and drug-loaded ST-4PC was assessed in mice and rats. Tumor growth inhibition was evaluated in LNCaP subcutaneous (s.c.) and LNCaP-luc orthotopic xenograft models. Using the s.c. model, mice were monitored weekly for weight loss, tumor volume (TV) and serum PSA. For the orthotopic model, mice were additionally monitored for bioluminescence as measure of tumor growth.

Results

ST-4PC demonstrated a sustained and steady release of incorporated drugs with 50% dtx and 20% bic being released after 14 days. While no systemic toxicity was observed, dose-dependent local side effects from dtx developed in the s.c. but not in the orthotopic model, illustrating the limitations of s.c. models for evaluating local cytotoxic therapy. In the s.c. model, 0.1%/4% and 0.25%/4% dtx/bic ST-4PC paste significantly reduced PSA progression, but did not have a significant inhibitory effect on TV. ST-4PC loaded with 1%/4% dtx/bic significantly reduced TV, serum PSA, and bioluminescence in the orthotopic xenograft model. Compared with drugs dissolved in DMSO, ST-4PC significantly delayed tumor growth.

Conclusion

Image-guided focal therapy using ST-4PC demonstrated promising inhibition of PSA progression and orthotopic tumor growth in vivo without significant toxicity, and warrants further clinical evaluation.

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Author notes

  1. These authors contributed equally: Claudia Kesch, Veronika Schmitt

Authors and Affiliations

  1. Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

    Claudia Kesch, Veronika Schmitt, Samir Bidnur, Marisa Thi, Eliana Beraldi, Igor Moskalev, Virginia Yago, Mary Bowden, Hans Adomat, Ladan Fazil & Martin E. Gleave

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    Veronika Schmitt & John K. Jackson

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  1. Claudia Kesch
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Correspondence to Martin E. Gleave.

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Conflict of interest

University of British Columbia has granted patents on the polymer paste formulation in ST-4PC, listing MEG, JKJ, VS, and CK as co-inventors, which have been outlicensed to Sustained Therapeutics, an early-stage biotech company founded by MEG.

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Kesch, C., Schmitt, V., Bidnur, S. et al. A polymeric paste-drug formulation for intratumoral treatment of prostate cancer. Prostate Cancer Prostatic Dis 23, 324–332 (2020). https://doi.org/10.1038/s41391-019-0190-x

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