Studies At Colorado State's Animal Tumor Center Point To Possible New Treatments For Variety Of Tumors In Humans
Tuesday, July 1, 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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