New Therapy For Prevention of Local Lung Tumor Recurrence

A team of engineers, chemists, and clinicians lead by Yolonda Colson, MD, PhD of Brigham and Women's Hospital and Mark W. Grinstaff, PhD of Boston University have developed a unique new drug delivery device for the prevention of lung tumor recurrence after surgical resection. Their research findings, titled, "Prevention of Local Tumor Recurrence Following Surgery Using Low Dose Chemotherapeutic Polymer Films" by Rong Liu, et al. was published online in the Annals of Surgical Oncology in December and is available in an upcoming print edition.

Although the most effective treatment for patients with localized non-small cell lung cancer is surgical resection, the long-term survival is poor if disease recurs. Even when recurrence is local, the majority of patients are not candidates for repeat surgery and the two-year survival rate is only 18 - 24 percent. In many patients, surgeons are often unable to obtain wide margins around the tumor due to poor cardiopulmonary function. Additionally, the administration of paclitaxel, the standard chemotherapy agent for lung cancer, has proved challenging in these patients due to the toxicity of the drug in healthy parts of the body and results showing that the accumulation of the drug in the diseased lung is poor with the standard intravenous delivery method.

In this study, researchers developed polymer films loaded with low dose chemotherapy that allowed the controlled release of the drug over an extended period of time to kill residual cancer cells left in the lung at the margin of the healthy lung tissue and the surgically resected tumor. These unique films are both flexible and easily stapled to tissue to allow local delivery, limiting the negative effects of chemotherapy on the rest of the body.

"This therapy has the potential to help thousands of lung cancer patients, who currently face a grim outlook when cancer recurs following surgical resection," said Yolonda Colson, MD, PhD, Associate Professor in Surgery and an attending cardiothoracic surgeon within the Division of Thoracic Surgery at Brigham and Women's Hospital. "When compared to the standard method of delivering paclitaxel, the local application of paclitaxel-loaded polymer films following surgical resection is an exciting new clinical possibility."

Researchers tested the effectiveness of the paclitaxel-loaded polymer films implanted in mice models over several weeks for the prevention of local tumor recurrence, impact on wound healing, and extent of local drug delivery. They found that the use of paclitaxel-loaded films after surgical resection of a lung cancer tumor prevented local tumor recurrence in 83.3% of cases. This was in comparison to the injection of paclitaxel at the surgical site in which tumor failed to grow after surgery only 22.2% of the time. They also found that the implantation of these films did not affect healing at the site of resection and that the concentration of paclitaxel was significantly higher in the tissue at the site of resection with the use of the films when compared to a standard systematic injection of the drug.

"This research project was unique because we were able to both design and synthesize a new polymeric drug delivery system and then evaluate that system in a clinically relevant model. This type of research collaboration between technology and medicine has the potential to impact patient care, which is extremely exciting" said Mark W. Grinstaff, professor of Biomedical Engineering and Chemistry at Boston University.

This research was supported by the Center for Integration of Medicine and Innovative Technology (CIMIT), the American College of Surgeons, and the Wallace H. Coulter Foundation.

Source: Brigham and Women's Hospital