Paclitaxel-loaded Mesh Reduces Local Recurrence of Lung Cancer in Animal Model

Investigators at Massachusetts General Hospital and elsewhere are interested in preventing local cancer recurrence by implanting drug-eluting materials at the resection site immediately after surgery.

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In Annals of Surgical Oncology, Mass General researchers previously demonstrated the efficacy of a polymer film implanted at surgical margins that released paclitaxel and significantly reduced local recurrence of lung cancer in mice. They have developed a polymer mesh for preventing recurrence with a faster drug release profile and that can be used with a surgical stapler.

Yolonda L. Colson, MD, PhD, chief of the Division of Thoracic Surgery, Lillian L. Tsai, MD, formerly a fellow in the Division, and colleagues report in The Annals of Thoracic Surgery that intraoperative placement of paclitaxel-loaded mesh significantly improved survival of mice bearing patient-derived xenografts of non–small-cell lung cancer.

Methods

The researchers harvested tumor tissue from a patient with a stage IV lung adenocarcinoma biopsy. Small pieces of the tissue, 3 to 5 mm³, were implanted subcutaneously into the backs of mice and allowed to grow.

The mice were randomized into four groups for subsequent treatment:

• Resection only (n=10)
• Resection + intraperitoneal (IP) paclitaxel (n=10)
• Resection + implantation of unloaded mesh (n=14)
• Resection + implantation of paclitaxel-loaded mesh (n=14)

The mice underwent preassigned treatment when the tumors reached 800 mm³ in volume.

Results

The mesh was sufficiently flexible and mechanically strong to enable facile implantation. When loaded with paclitaxel, the mesh was associated with prolonged drug delivery and significantly improved survival:

Local recurrence-free survival

• Resection only—median 24 days
• IP paclitaxel—24 days
• Unloaded mesh—28 days
• Paclitaxel-loaded mesh—Not reached (P<0.0001)

Overall survival

• Resection only—median 63 days
• IP paclitaxel—62 days
• Unloaded mesh—55 days
• Paclitaxel-loaded mesh—Not reached (P=0.0006)

On day 120, the mice treated with the paclitaxel-loaded mesh no longer had mesh present. Healthy skin and muscle tissue surrounded the implantation site, and no organ examined showed evidence of systemic toxicity from the mesh.

Envisioning the Future

The researchers believe flexible drug-loaded meshes would have multiple benefits because they could be:

• Placed intraoperatively at sites with limited or "close" margins
• Either sutured or stapled (in another experiment, the mesh was successfully stapled to bovine lung tissue)
• Loaded with one of a selection of drugs (the Mass General team has also manufactured meshes that release pemetrexed, eupenifeldin, or doxorubicin)
• Useful for treating esophageal, colon, and breast cancers, as well as lung cancer

In the future, xenografts from a patient's tumor sample from a preoperative biopsy might be used to predict that individual's response to a specific drug. Thus, the mesh could be formulated with the appropriate drug for personalized treatment to prevent local recurrence.

The Mass General researchers are currently conducting large-animal studies using the meshes and hope to bring them to clinical trials.

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