Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films
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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.
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.
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).
Local application of paclitaxel-loaded polymer films following surgical resection can prevent local tumor recurrence without impairing wound healing.
KeywordsPaclitaxel Drug Release BCNU Lewis Lung Carcinoma Local Tumor Recurrence
Y.L.C. is supported by the Center for Integration of Medicine and Innovative Technology (CIMIT grants 06-006, 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 Dr. Paul Catalano of the Dana-Farber/Harvard Cancer Center for his statistics consulting, the Animal Resources Facility at Dana-Farber Cancer Institute, and Jessica Rickards for assistance with document preparation.
None of the authors have conflict of interest.
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