The leading cause of cancer mortality in the U.S., lung cancer is remarkably difficult to cure. The standard of care is to surgically remove, or resect, lung tissue tumors, but nearly 40 percent of patients receiving such treatment at an early stage develop recurrent disease at a local or distant site. Even when recurrence is local, the majority of patients are not candidates for repeat surgical resection, and the two-year survival rate is only 18 to 24 percent. Finally, systematic injection of paclitaxel, the standard chemotherapy agent for lung cancer, delivers inadequate concentrations of the drug to diseased lung tissue and damaging toxins to healthy organs.
Joining forces to resolve these problems, a team of engineers, chemists and clinicians led by Professor Mark W. Grinstaff (BME, Chemistry) and Yolonda L. Colson, associate professor of surgery and an attending cardiothoracic surgeon at Brigham and Women’s Hospital, has developed a unique new drug delivery device for the prevention of lung tumor recurrence after surgical resection. Grinstaff group member Jesse B. Wolinsky (BME PhD’09) was instrumental in the development and demonstration of the concept.
In a study published in the online edition of Annals of Surgical Oncology in December, the research team produced paclitaxel-loaded polymer films that allowed the controlled, low-dose release of the drug over an extended period to kill cancer cells remaining in lung tissue after surgical resection of mouse lung tumors. The films are flexible and easily stapled to tissue to allow local delivery, limiting the negative effects of chemotherapy on the rest of the body.
“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,” said Grinstaff. “This type of research collaboration between technology and medicine has the potential to impact patient care, which is extremely exciting.”
Grinstaff’s group focused on designing a polymer that could be stapled into diseased lung tissue and deliver a chemotherapeutic drug to tumor cells over several weeks—all while buttressing the tissue to promote efficient healing. The group tested different polymer materials in vitro and selected one polymer formulation for evaluation in an in vivo mouse model developed by Colson, a lung cancer expert.
Implanting the paclitaxel-bearing films in mouse models over several weeks, the researchers found that the use of paclitaxel-loaded films after surgical resection of a lung cancer tumor prevented local tumor recurrence in 83.3 percent of cases—compared to a 22 percent rate when paclitaxel was injected at the surgical site. They also found that the implantation of these films did not inhibit 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 therapy has the potential to help thousands of lung cancer patients, who currently face a grim outlook when cancer recurs following surgical resection,” said Colson. “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.”
Over the next two years, the research team plans to perform experiments to monitor the release and concentration of a chemotherapeutic agent in treated tissue. Once they determine that the polymer they’re using is safe and able to deliver the drug locally without systemic side effects, they will conduct a pilot clinical trial.
According to Grinstaff, the film-based drug delivery system is easily adaptable for clinical use. “The technology that we’re developing can be integrated into the standard device that surgeons use to cut and staple lung tissue during resection” he said.
The research was supported by the Center for Integrative Medicine and Innovative Technology (CIMIT), a nonprofit consortium of hospitals and engineering universities supporting translational research; the American College of Surgeons, and the Wallace H. Coulter Foundation.
This article is partly based on a press release issued by CIMIT.