Studies At Colorado State University's Animal Tumor Center Point To New Treatments For Cancer In Humans

June 30, 1997

FORT COLLINS--A breakthrough treatment that helps eliminate bone cancer in dogs may show promise in the battle against other types of human cancer, including breast cancer.

Colorado State University veterinary researchers are using biopolymers--porous, sponge-like materials that slowly deliver chemotherapy directly to cancer cells, then biodegrade--to treat a variety of cancers in dogs. A chemotherapeutic agent, cisplatin, is added to the polymer, which releases a constant dose through a patented drug-delivery system known as open-cell polylactic acid, or OPLA. Researchers hope the successful treatment of dogs with cancer using this method can be applied to treating humans with local tumors.

Drs. Stephen Withrow, chief of Colorado State's clinical oncology services, and William Dernell, assistant professor of surgical oncology, have completed preliminary studies of breast cancer in mice that show implanted polymers are more effective in eliminating local cancer than chemotherapy administered by injection, the most common method for cancer patients.

This study and other research under way at the Veterinary Teaching Hospital points to the possibility of alternative treatments for breast cancer that are less expensive and less toxic than traditional forms of chemotherapy and radiation. Withrow explained that radiation therapy costs as much as $10,000 and may produce significant side effects in some patients. But, because polymers deliver a slow but constant dose of chemotherapy to a targeted area, patients can receive a much higher local dose than they can intravenously without experiencing whole body symptoms.

"It's a unique way of attacking a tumor," Withrow said. "Based on our success in treating dogs with bone cancer using this method, we are now focusing on how we can apply our findings to breast cancer, which is the leading cause of cancer death among women aged 40 to 55 and causes more than 40,000 deaths in the United States annually."

In a preliminary study, researchers tracked 42 female mice injected with fast-growing breast cancer cells. All of the mice underwent surgery to remove the bulk of the tumor, then were divided into three experimental groups. The first group received no post-operative treatment, while the second received doses of cisplatin through the abdomen, which is similar to intravenous treatment. The third group was treated with the cisplatin polymer. The results of the study were:

The polymer-delivered chemotherapy eliminated all local regrowth of cancer and prevented it from spreading to the lungs. In half the mice that received chemotherapy through the abdomen, cancer returned to the breast but did not spread.

Most of the mice that received surgery but no chemotherapy had local tumors recur and spread to other parts of the body.

Results from this preliminary work prompted the research team to take on a more extensive study of 180 female mice to determine whether longer exposures to the drug--either through the polymer or intravenously--changes the way remaining cancer cells react.

That study, now under way, also will analyze whether adding other time-release drugs--such as a compound to stimulate the body's immune system and promote healing--make polymer treatments even more effective.

FUTURE HOLDS NEW AND MORE EFFECTIVE CANCER DRUG THERAPIES

Withrow and Dernell believe polymers could eventually serve not only as a vehicle to deliver chemotherapy, but to administer antibiotics and even hormones to encourage tissue regrowth in a timed sequence of releases.

"This opens a wide range of possibilities in developing new drugs to fight cancer and heal the body from the inside without producing the toxic effects of traditional chemotherapy and radiation," Dernell said. "There's still a lot we don't know and we have a long way to go, but these studies represent a promising new direction for available cancer treatments."

Withrow, Dernell and other members of the oncology research team base its premise on the Veterinary Teaching Hospital's success in treating dogs with osteosarcoma, a bone disease that often resulted in limb amputation and death. Today, surgeons remove the diseased bone and replace it with healthy bone, then implant several pieces of the chemotherapy-rich polymer--developed by Colorado State veterinary researchers in conjunction with a private biomedical firm--before closing the wound.

About 30 percent of dogs that receive limb sparing surgery and polymer chemotherapy experience local recurrence after one year, compared to 60 percent local recurrence in dogs that do not receive the polymer. More than 200 dogs with a variety of cancers, including osteosarcoma and soft tissue tumors, have received this breakthrough treatment at Colorado State's world-renowned oncology unit since 1986.

Other related studies this summer at Colorado State will look into different types of polymers and drugs in the fight against cancer, Dernell added. Although square-shaped polymers work well in treating bone cancer in dogs, they do not always fill the area remaining after soft tissue tumors are removed. As a result, the drug may not always be adequately distributed to remaining cancer cells.

This summer, Colorado State's veterinary researchers will join Mark Manning at the University of Colorado's School of Pharmacy to develop a gel polymer that can be injected into the cavity left after surgery and fully absorbed by surrounding tissue. Colorado State and CU scientists also will study ways to use new cancer-fighting drugs in a polymer gel system.

"Many of the treatments we develop for cancers in dogs have direct applications to treating cancers in humans," Withrow said. "We hope this technique will prove to be a useful and novel treatment in the fight against cancer and that it may lead to a whole new era of cancer drug therapy."

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Colorado State University

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