A PUBLICATION FOR FRIENDS OF DUKE COMPREHENSIVE CANCER CENTER DukeComprehensive CancerCenter Summer 2002 notes New Breast Cancer Therapy Boosts Drugs’ Effects, Dramatically Shrinks Tumors by Becky Levine Kimberly Blackwell, MD and Ellen L. Jones, MD atients of Dr. Kimberly into normal tissues over a period (heat therapy) together with Second, heat increases the rate Blackwell jokingly call their of three or four weeks—long chemotherapy and fat liposomes of a drug’s uptake into the cancer P treatment table the “booby enough for the liver and spleen in patients with newly diagnosed, cell itself, through mechanisms Jacuzzi.” The name may be a bit to blunt its toxic side effects. large and invasive breast tumors. that are not well understood. Heat crass, but then, a close brush with In several cases, the treatment While hyperthermia has long also increases oxygen levels within mortality entitles these women to has remarkably destroyed all been known to boost the effects the tumor, oxygen being critical to call the life-saving contraption visible signs of the tumor. In of radiation therapy, its ability to the proper functioning of many whatever they want. others, the treatment has saved enhance a tumor’s response to chemotherapy agents, including All humor aside, they have come women’s breasts from surgical drugs encased in liposomes is just those in the current trial. And to the Duke Comprehensive removal. In every case, it has being explored in humans. finally, heat amplifies the level of Cancer Center with the earnest halted the tumor from growing, Already, the Duke researchers DNA damage that chemotherapy hope of preserving their lives, if said Blackwell, a Duke medical have shown that traditional inflicts upon the cell by inhibiting not their breasts, from the ravages oncologist who runs the protocol chemotherapy agents, which have enzymes that normally repair of deadly breast cancers—termed with a team of a dozen colleagues. little effect on cancer in mice, are such DNA damage. “inflammatory” and “locally The results are far more dramatic highly effective in mice when Hyperthermia, however, is not advanced” tumors—that often resist than any of the team envisioned, encapsulated in liposomes and the only powerhouse in this new traditional treatments. Sixty to 70 based on their pre-clinical studies, heated, said Mark Dewhirst, PhD, treatment equation, said Dewhirst. percent of its victims do not survive said Blackwell, who presented their director of the hyperthermia Liposomes themselves are quite past five years. Twenty-one women phase I clinical trial data on May 18 program at Duke. beneficial to patients because their came to Duke for a unique phase I at the American Society of Clinical Simple as it appears, heat trig- unique formulation reduces the trial in search of better odds. Oncology in Orlando. Twenty-one gers a series of complex events amount of drugs that enter the Propped on pillows and sere- women with newly diagnosed that are critical to the tumor’s heart, nerves and other critical naded by the music of their choice, breast cancers participated in the demise, said Dewhirst, whose tissues, where they could cause the women lie upon a massage- 12-week hyperthermia trial, funded decades of animal research gave substantial harm. like table for one hour as radio by the National Cancer Institute. rise to the current trial. First, heat- The liposomal hyperthermia frequency energy warms their “Encapsulating the chemother- ing the breast draws liposomes out combination appears to be quite breasts, which lie in a sunken pool apy inside of liposomes enables of the bloodstream and directly to effective thus far. Results show of water. The heat triggers the us to deliver 30 times more the site of the tumor, thus concen- the combined therapy has halted chemotherapy they have just chemotherapy than we normally trating the drug-packed liposomes tumor growth in all women and received to settle inside the tumor, could to the tumor site, without where they are needed the most. has at least partially shrunk tumors where it trickles out of its protec- poisoning the rest of the body,” “A tumor’s blood vessels are in half the women. Eleven percent tive coating—a tiny fat bubble said Blackwell. “Heat also boosts much leakier than normal blood of women have had complete called a liposome—and attacks the drugs’ potency by interfering vessels,” Dewhirst said. “Heat pulls pathologic responses, meaning no the tumor’s genetic machinery. with mechanisms that control a the blood vessels apart even more cancer was found in the breast The body’s normal tissues cancer cell’s ability to replicate.” than usual, allowing tiny particles tissue upon analyzing its surgical remain unheated, so the drug is The only clinical trial of its kind —such as liposomes—to leak remains. Thirty-three percent of not preferentially delivered there. in the nation, Blackwell said it is out and pool into the tumor’s patients had complete clinical Hence, the drugs slowly leak out the first to combine “hyperthermia” interstitial spaces.” responses, meaning visible signs of Continued on page 8 DUKE COMPREHENSIVE CANCER CENTER Darell D. Bigner, MD, PhD, Stepping Down named Director pro tempore Michael Colvin, MD, arell D. Bigner, MD, PhD, announced in January has been named Director pro tempore of the Duke . his decision to step down D O Comprehensive Cancer Center as from the directorship in order to national search for a new director return full time to cancer research. takes place. Bigner is the Edwin L. Colvin had been director of the Jones, Jr. and Lucille Finch Jones Duke Comprehensive Cancer Center Cancer Research Professor of for more than six years. Pathology, Chief of the Division of In 1995, Colvin became the third Basic Science and Investigative director of the Duke Comprehensive Pathology, and Director of the Preuss Darell D. Bigner, MD, PhD Cancer Center. He was recruited to Laboratory for Brain Tumor Duke after a 34-year career at Johns Research. He was Deputy Director of the Cancer Center. Hopkins, where he was chief of the Dr. Bigner came to Duke in 1963 as a medical student and has remained internationally recognized Division of Pharmacology and for the past 38 years. He is considered the leading authority on brain tumors, Experimental Therapeutics. and has directed the neuro-oncology program for the past 25 years, building it into the largest and most successful of its type in the world. Under his Colvin is one of the country’s truly outstanding cancer direction, Duke’s program obtained the first Brain Tumor Center grant for researchers, and is well known for his pioneering work with the National Institute of Neurological Diseases and Stroke, and it remains cyclophosphamide and other drugs that damage the genetic one of three programs in the nation with such a grant. material that causes cancer cells to replicate. He was one of the “The Duke Comprehensive Cancer Center is now one of the top first investigators to use very high dose of cyclophosphamide for centers for research and care in the country, and I am confident that the treatment of solid tumors, now a common practice in bone we can ensure our Cancer Center will remain a national leader as we marrow transplantation for breast cancer and other tumors. conduct the search for Mike Colvin’s successor,” Bigner said. ● During his tenure, Colvin did much to strengthen the Cancer Center. He restructured the administration and appointed leaders to oversee major areas such as basic research, clinical research, and cancer prevention, detection and control Herman Albert, Cancer research. One of Colvin’s primary goals was to develop multi- disciplinary disease-specific programs that brought together Center Benefactor, Dies physicians and scientists from different fields to look at specific erman Albert died Sunday, June 16, cancers. The Brain Tumor Center, the breast cancer program, 2002, at Duke University Medical and the thoracic oncology program are incredible examples HCenter. Last year the Alberts, who live of this approach, which enables our patients to benefit from in Purchase, NY, and Palm Beach, Fla., gave Duke’s world-class laboratory research as soon as the new $1.5 million to the Thoracic Oncology Program therapies are available. to establish the Herman and Ruth Albert Lung He also brought together collaborators to develop innova- Cancer Genomics Fund. Earlier this year, they tive therapies such as cancer vaccines and created a drug committed an additional $2 million to the fund, development program to create and test new treatments. a gift which came as a part of a $10 million He broadened the scope of the adult bone marrow transplan- commitment to the Medical Center, $8 million tation to include other diseases and add a stronger of which will create he Ruth and Herman Herman Albert immunotherapy component. Albert Eye Institute. Under his direction, the Cancer Center received an “out- Supporters of Duke with their time and resources, both Mr. and Mrs. Albert were members of Duke Cancer Center and Medical Center standing” score by the National Cancer Institute on its most Advisory Boards. recent core grant renewal and peer review. The Center was Ralph Snyderman, MD, Chancellor for Health Affairs, and CEO granted $3.5 million in support, a figure that represents a 38% of the Duke University Health System, called Herman Albert “a truly increase over previous years. great man, one of the strongest I’ve ever known. The legacy that he Colvin was committed to meeting the needs of cancer and Ruth created at Duke will live and benefit the health and lives of patients. He oversaw the expansion of the Jaycees Outpatient generations to come.” Treatment Facility and has been a staunch supporter of the Herman Albert was born on November 23, 1922.