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01-01-2012 | Bone and Soft Tissue Sarcomas

Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy

Authors: Rong Liu, MD, PhD, Jesse B. Wolinsky, PhD, Paul J. Catalano, ScD, Lucian R. Chirieac, MD, Andrew J. Wagner, MD, PhD, Mark W. Grinstaff, PhD, Yolonda L. Colson, MD, PhD, Chandrajit P. Raut, MD, MSc

Published in: Annals of Surgical Oncology | Issue 1/2012

Abstract

Background

Locoregional recurrences occur in up to 50% of patients after macroscopically complete (R0/R1) resections of abdominal, pelvic, and retroperitoneal sarcomas. Efficacy of a drug-eluting polymer film in reducing locoregional recurrence rates was assessed in a murine recurrent sarcoma model.

Methods

Poly(glycerol monostearate-co-caprolactone) polymer films were synthesized with and without 300 μg paclitaxel (Pax-film and unloaded film). Cytotoxicity was assessed against CS-1 (human chondrosarcoma) cells in vitro and in vivo in nude mice. Following R0/R1 resection of primary subcutaneous tumors, mice were blindly randomized to: (1) Pax-film implant, (2) unloaded film implant, (3) paclitaxel 300 μg IV (Pax IV), or (4) no other therapy (“untreated”). Locoregional recurrence, overall survival (OS), and tumor mitotic index were evaluated.

Results

Pax-films, but not unloaded films, reduced CS-1 viability in vitro for >50 days (P < 0.001). In vivo, locoregional recurrence was observed in 2 of 12 Pax-film mice (17%), 9 of 13 unloaded film mice (69%), 8 of 9 Pax IV mice (89%), and 7 of 8 untreated mice (88%) (P < 0.01). Median OS was 81, 64, 48, and 56 days, respectively. Paclitaxel levels in local tissues were 50- to 300-fold greater in Pax-film mice compared with Pax IV mice. Tumor mitotic index adjacent to Pax-films was significantly lower than adjacent to unloaded films.

Conclusions

Tumor bed implantation of Pax-films after R0/R1 resection is superior to Pax IV as evidenced by reduced locoregional recurrence and improved OS in a murine recurrent sarcoma model. Continuous local drug exposure via polymer films represents a potentially novel approach for treatment of locally aggressive sarcomas.

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Title: Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy
Authors: Rong Liu, MD, PhD
Jesse B. Wolinsky, PhD
Paul J. Catalano, ScD
Lucian R. Chirieac, MD
Andrew J. Wagner, MD, PhD
Mark W. Grinstaff, PhD
Yolonda L. Colson, MD, PhD
Chandrajit P. Raut, MD, MSc
Publication date: 01-01-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 1/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-1871-4

At a glance: The STEP trials

Springer Medicine

Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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