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

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgment

C.P.R. is supported by funding from the Department of Surgery, Brigham and Women’s Hospital. Y.L.C. is supported by the Center for Integration of Medicine and Innovative Technology (CIMIT grant 07-004, and 09-433), the American College of Surgeon’s George H. A. Clowes, Jr., MD, FACS, Memorial Research Career Development Award. M.W.G. is supported by the Wallace H. Coulter Foundation. We thank the Animal Resources Facility at Dana-Farber Cancer Institute for the high-standard of care given to our animals, Joshua H. Winer, M.D. and Jacqueline E. Wade, B.S. for technical assistance, and Francis Hornicek, M.D. for use of the CS-1 cell line.

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Authors and Affiliations

  1. Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Rong Liu MD, PhD, Yolonda L. Colson MD, PhD & Chandrajit P. Raut MD, MSc

  2. Departments of Chemistry and Biomedical Engineering, Boston University, Boston, MA, USA

    Jesse B. Wolinsky PhD & Mark W. Grinstaff PhD

  3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Paul J. Catalano ScD

  4. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Lucian R. Chirieac MD

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Andrew J. Wagner MD, PhD

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  1. Rong Liu MD, PhD
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Correspondence to Mark W. Grinstaff PhD, Yolonda L. Colson MD, PhD or Chandrajit P. Raut MD, MSc.

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Liu, R., Wolinsky, J.B., Catalano, P.J. et al. Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy. Ann Surg Oncol 19, 199–206 (2012). https://doi.org/10.1245/s10434-011-1871-4

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  • DOI: https://doi.org/10.1245/s10434-011-1871-4

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