Annals of Surgical Oncology

, Volume 19, Issue 1, pp 199–206

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

Authors

  • Rong Liu
    • Department of SurgeryBrigham and Women’s Hospital
  • Jesse B. Wolinsky
    • Departments of Chemistry and Biomedical EngineeringBoston University
  • Paul J. Catalano
    • Department of Biostatistics and Computational BiologyDana-Farber Cancer Institute
  • Lucian R. Chirieac
    • Department of PathologyBrigham and Women’s Hospital
  • Andrew J. Wagner
    • Department of Medical OncologyDana-Farber Cancer Institute
    • Departments of Chemistry and Biomedical EngineeringBoston University
    • Department of SurgeryBrigham and Women’s Hospital
    • Department of SurgeryBrigham and Women’s Hospital
Bone and Soft Tissue Sarcomas

DOI: 10.1245/s10434-011-1871-4

Cite this article as:
Liu, R., Wolinsky, J.B., Catalano, P.J. et al. Ann Surg Oncol (2012) 19: 199. doi:10.1245/s10434-011-1871-4

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.

Supplementary material

10434_2011_1871_MOESM1_ESM.doc (971 kb)
Supplementary material 1 (DOC 971 kb)

Copyright information

© Society of Surgical Oncology 2011