Breast Cancer Therapy Heats Up
May 18, 2002 -- A heat-targeted breast cancer therapy under study at Duke University Medical Center has shown dramatic results that could represent a major advance in treating breast cancer and other cancers, as well.
Duke researchers say responses from an early study of the therapy were more dramatic than they could have envisioned. Twenty-one women with hard-to-treat inflammatory or locally advanced breast tumors took part in the study. Several had complete responses, meaning no visible signs of tumor remained; others had tumor shrinkage that allowed their breasts to be saved; and none of the women experienced tumor growth while receiving the treatment.
The therapy involves heating the breasts to a specific temperature immediately after chemotherapy is given to help direct the targeted therapy to the tumor sight. This is achieved by immersing the breasts in salt water for an hour, as radio frequency energy warms the tumor to 104 degrees Fahrenheit. The chemotherapy is encapsulated in fat bubbles, known as liposomes, which have been engineered to melt and release the tumor-targeting drugs at this temperature.
Patients jokingly refer to the contraption used in their treatment as the "booby Jacuzzi."
Duke cancer specialist Kimberly Blackwell, MD, tells WebMD that the technology behind the heat-targeted approach has been developed at Duke over several decades. Liposomes reduce damage to healthy cells by targeting drug therapy to tumors. The heat-sensitive liposomes developed by Duke researchers Mark Dewhirst, PhD, and David Needham, PhD, allow the drugs to not only be delivered to a specific site, but released at a specific temperature.
The Duke study is one of the first to combine heat therapy with liposomes. Blackwell was scheduled to discuss the study today at the annual meeting of the American Society of Clinical Oncology in Orlando.
"We know that we can kill cancer cells in the lab, but we have been frustrated by the fact that these cures often don't work so well in people," Blackwell says. "It may be that we have done a lousy job of getting the chemotherapy where it needs to go. The principle here is that by improving the delivery of chemotherapy, we will enable these drugs to do what they need to do."
Blackwell says the approach seems to work because heat stimulates blood flow, and the blood flow directs the intravenously introduced drug therapy to the tumor site. In addition, when blood vessels are heated they become more porous, allowing easier access to the tumor.
Because of the targeted approach, participants experienced less nausea, fatigue, and toxicity to the heart than is commonly seen with traditional chemotherapy, even though some of the patients received higher than normal doses of the drugs Adriamycin and Taxol.
"This is especially exciting because when non-liposomal [Adriamycin] and Taxol are combined, there is often cardiac toxicity," Blackwell says.
Half of the women had some tumor shrinkage, one-third had no evidence of tumor remaining, and 17% were able to undergo breast-saving surgery following chemotherapy. Most of the women participating in the trial were not considered candidates for surgery of any kind at diagnosis.
The Duke researchers are planning a phase II study involving 40 breast cancer patients, using the highest drug dosage given during the phase I trial. Blackwell tells WebMD that the approach may also have applications for the treatment of ovarian, prostate, and head and neck tumors.
"Encapsulating the chemotherapy inside of liposomes enables us to deliver 30 times more chemotherapy than we normally could to the tumor site without poisoning the rest of the body," Blackwell says. "Heat also boosts the drugs' potency by interfering with mechanisms that control a cancer cell's ability to replicate."
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