Annals of Surgical Oncology

, Volume 17, Issue 4, pp 1203–1213

Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films

  • Rong Liu
  • Jesse B. Wolinsky
  • Joseph Walpole
  • Emily Southard
  • Lucian R. Chirieac
  • Mark W. Grinstaff
  • Yolonda L. Colson
Translational Research and Biomarkers

DOI: 10.1245/s10434-009-0856-z

Cite this article as:
Liu, R., Wolinsky, J.B., Walpole, J. et al. Ann Surg Oncol (2010) 17: 1203. doi:10.1245/s10434-009-0856-z

Abstract

Aim

To evaluate the efficacy of a polymer film designed for prolonged paclitaxel release at surgical margins to prevent local recurrence in non-small-cell lung cancer (NSCLC) following complete surgical resection in a murine model.

Methods

Poly(glycerol monostearate co-ε-caprolactone) polymer films were prepared with or without 10% (w/w) paclitaxel and characterized for prolonged tumor cytotoxicity in vitro against several NSCLC cell lines including LLC, NCI-H460, and NCI-H292. Films were implanted following complete LLC tumor resection and assessed in vivo for prevention of local tumor recurrence, impact on wound healing, and extent of local drug delivery. Plasma and local tissue concentrations of paclitaxel were compared following systemic administration and film implantation.

Results

The flexible polymeric films eluted paclitaxel over several weeks and remained cytotoxic to LLC, NCI-H460, and NCI-H292 cells in vitro for 50 days, while unloaded films did not impair tumor cell growth. Implanted paclitaxel films prevented local tumor recurrence in vivo in 83.3% of animals, compared with unloaded films (12.5%), systemic (22.2%) or locally administered paclitaxel (0%) (P < 0.005). Although minimal paclitaxel remained in either plasma or tissue 10 days after systemic injection, local paclitaxel concentration at the site of surgical resection was significantly greater (3,000-fold) at 10 days when paclitaxel was locally delivered via films (P = 0.024).

Conclusions

Local application of paclitaxel-loaded polymer films following surgical resection can prevent local tumor recurrence without impairing wound healing.

Supplementary material

10434_2009_856_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 49 kb)

Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Rong Liu
    • 1
  • Jesse B. Wolinsky
    • 2
  • Joseph Walpole
    • 1
  • Emily Southard
    • 1
  • Lucian R. Chirieac
    • 3
  • Mark W. Grinstaff
    • 2
  • Yolonda L. Colson
    • 1
  1. 1.Division of Thoracic Surgery, Department of SurgeryBrigham and Women’s HospitalBostonUSA
  2. 2.Department of Biomedical Engineering and ChemistryBoston UniversityBostonUSA
  3. 3.Department of PathologyBrigham and Women’s HospitalBostonUSA