Prevention of local tumor recurrence following surgery using low-dose chemotherapeutic polymer films.
OBJECTIVE
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-epsilon-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.
Liu
Rong
R
Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Wolinsky
Jesse B
JB
Walpole
Joseph
J
Southard
Emily
E
Chirieac
Lucian R
LR
Grinstaff
Mark W
MW
Colson
Yolonda L
YL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood; D011108:Polymers / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D017239:Paclitaxel