Paclitaxel-Loaded Polymer Film Prevents Local Recurrence of Non-Small Cell Lung Cancer
Rong Liu1, Jesse Wolinsky2, Mark W. Grinstaff2, Yolonda L. Colson1; 1Brigham and Women's Hospital, Boston, MA; 2Boston University, Boston, MA
Objective: Surgical resection remains the most effective treatment option for patients with non-small cell lung cancer; however medical comorbidities and poor pulmonary reserve often limit the extent of resection. Unfortunately, limited resections are associated with 2-3 times higher rates of locoregional recurrence, suggesting that microscopic disease is present near the resection margin. Therefore, the focus of this study is to establish proof of concept that the implantation of biocompatible paclitaxel-loaded polymer films at the time of tumor resection can prevent local recurrence.
Methods: Poly(ester-co-carbonate) films (1.0x0.8 cm2) were synthesized onto bovine pericardial strips with or without the addition of 30μg paclitaxel (Pax-film or unloaded film, respectively). The subcutaneous injection of 7.5 x 105 Lewis Lung Carcinoma (LLC) cells on the dorsum of C57BL/6J female mice resulted in development of the primary tumor. A complete resection of the primary tumor was performed and Pax-loaded and unloaded polymer films were randomly assigned for implantation at the site of surgical resection prior to wound closure.
Results: Primary subcutaneous tumor resections were performed 10-18 days after injection of LLC. There was no difference in the average tumor size (588±160 vs 581±96 mm3) between mice that subsequently received unloaded films or Pax-films. All mice treated with unloaded films (n=3) had visible local recurrence at the site of the film at 7.3±1.8 days after resection and required sacrifice secondary to large locally recurrent tumor by 15.6±1.5 days. In contrast, there was no evidence of locally recurrent disease at the site of Pax-films in any of the recipient mice (n=4) at 20 days (p<0.05 vs unloaded films, Fisher Exact Test; Figure). Similarly, survival was markedly prolonged before Pax-films recipients eventually succumbed to progressive metastatic disease from the primary tumor (27.0±2.0 days; p<0.01 vs unloaded films, t-test).
Conclusion: Implantation of Pax-films at the time of surgical resection can prevent local tumor recurrence and prolong survival in a subcutaneous LLC tumor model in mice, without significant impairment in wound healing. These findings suggest that Pax-loaded polymer films incorporated at the surgical margin, may afford enhanced local drug delivery aimed at preventing the growth of occult disease present following parenchyma-sparing surgery, and offer the means to decrease local recurrence rates in patients with stage I lung cancer in the future.
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