Research Notes II
A relentless attack on tumor's blood supply
Researchers are combining a regimen of constant, low-dose chemotherapy with an antiangiogenesis drug to attack advanced breast cancer in a new clinical trial at Dana-Farber. Both prongs of the attack are aimed at starving the cancer by destroying its blood supply, rather than attempting to kill the tumor cells directly. This strategy has the potential to control cancer by blocking the dense network of blood vessels that tumors recruit from surrounding tissues, a process called angiogenesis.
The new trial, opening in the summer of 2003, is headed by Harold J. Burstein, MD, PhD, of the Women's Cancers Program, and collaborators include Lyndsay Harris, MD, and David Spigel, MD, a third-year fellow, who has worked in the breast oncology group. Also collaborating in the trial is John Heymach, MD, PhD, a DFCI fellow currently doing research in the laboratory of Judah Folkman, MD, of Children's Hospital Boston, who pioneered the concept of antiangiogenic therapy.
Avastin and metronomic therapy are aimed at blocking the blood vessels a tumor develops to nourish its growth and spread.
Illustration by Johnb DiGianni
Standard chemotherapy drugs are intended to poison the tumor, but they also damage its nourishing web of blood vessels, researchers have found.
Customarily, doctors administer chemotherapy for a limited time at the highest dose the patient can tolerate, then stop and allow the body to recover for several weeks. During this period, however, the tumor has a chance to rebuild the damaged blood supply network, aiding the cancer's growth.
In the new trial, patients will receive chemotherapy doses that are a fraction of the standard dose, but they will receive them every day to keep angiogenesis at a minimum. This clockworklike regimen has been dubbed " metronomic," because it is as regular and constant as a ticking metronome.
The second half of this one-two punch is an antiangiogenesis drug called Avastin, which is designed to block a growth factor that spurs the development of blood vessels around tumors. The cancer community recently learned that the drug had lengthened survival of metastatic colon cancer patients in a Phase III clinical trial. However, Avastin hadn't been effective in a previous trial of patients with advanced breast cancer, but " maybe that was because the patients were treated too late in the course of their disease," suggests Dr. Burstein.
Patients entering the new trial will have had less prior treatment for their metastatic cancer, meaning their disease is less advanced than in the previous trial. They will also be receiving the metronomic chemotherapy in addition to Avastin.
" We are very excited about this trial. The laboratory models suggest this is an effective way to combat cancer," says Dr. Burstein. " We think it is an innovative approach and expect it to be well tolerated by patients." Patients will also be treated at the Sarah Cannon Cancer Center in Nashville, Tenn.
The Avastin trial will be open to patients with metastatic breast cancer who have received no prior chemotherapy for advanced disease, or one prior chemotherapy regimen. Interested parties can call (617) 632-3478. The trial, expected to continue for 18 to 24 months, is supported by the federal breast cancer SPORE (Specialized Program of Research Excellence) grant to Dana-Farber and by the Avon Foundation. As Eric Winer, MD, director of the Breast Oncology Center, notes, " The trial is innovative in its approach, rooted in solid laboratory science, and may help lead the way to a new approach to breast cancer treatment."
