PHILADELPHIA INTERNATIONAL MEDICINE® NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
February 21, 2004

In this month's edition:

1. Jefferson Researchers Find Immune Response and Dosing Keys to Vaccine's Success Against Melanoma
2. University of Pennsylvania Breast Cancer Vaccine Study Supported by Unique "Progress for Patients" Grant from Avon and National Cancer Institute
3. Fox Chase Cancer Center "Tailors" Radiation Therapy To Help Reduce Erectile Dysfunction in Men Treated for Prostate Cancer

Editor's Note: Three of the leading cancer centers in the United States are part of the Philadelphia International Medicine network. The Comprehensive Cancer Centers at Fox Chase Cancer Center, Thomas Jefferson University Hospital and the University of Pennsylvania Medical Center are each researching new cures and treatment protocols to combat this deadly disease. In this month's issue of the Philadelphia International Medicine News Bureau, we are focusing on new findings regarding cancer prevention and treatment. For more information, or to schedule an appointment, please call PIM at 215-735-3575.

Jefferson Researchers Find Immune Response and Dosing Keys to Vaccine's Success Against Melanoma

Philadelphia - How well a patient's immune system reacts to his own cancer cells and the schedule by which the vaccine is given are two key factors in the success of a custom-made vaccine created from the cancer cells of patients with malignant melanoma, the deadliest form of skin cancer and fastest growing cancer in the United States.

Nearly one-half - 44 percent - of malignant melanoma patients enrolled in a clinical trial who received the vaccine following standard surgery lived at least five years - no small achievement, considering that only about 20 percent live that long with surgery alone, according to David Berd, MD, professor of medicine at Jefferson Medical College of Thomas Jefferson University and Jefferson's Kimmel Cancer Center, part of Philadelphia International Medicine.

"Although additional, controlled trials will be necessary to prove efficacy, these numbers look promising," says Berd, who created the vaccine. "We're emphasizing what we call the immunopharmacology of our cancer vaccine, meaning that how the vaccine is administered and the immune response that it elicits strongly influence whether or not a patient will survive five years."

He and his colleagues report their findings in the current issue of the Journal of Clinical Oncology. An editorial accompanies the paper.
The phase II trial examined the immunological and clinical results of a vaccine given to 214 melanoma patients with clinical stage III disease, meaning it had spread to lymph nodes that were large enough to be felt by routine examination.

The vaccine was prepared from each patient's own cancer cells. Before injecting the cells into patients, they were inactivated and modified with a chemical, dinitrophenyl (DNP). It is believed that the chemically-altered cells make the cancer cells more visible to the body's immune system, which recognizes and reacts against them.

According to Berd, the immune response against the cancer cells is measured by a test called delayed-type hypersensitivity (DTH), which is similar to a tuberculosis or allergy test. Patients who developed stronger DTH - indicating an aroused immune system - to their own tumor cells after receiving the vaccine lived twice as long as those who did not.

The way the vaccine was administered mattered to patients as well. The vaccine was given in four different dosing schedules, but the researchers discovered that a particular dosing schedule elicited the maximum immunological response. His group found that if a certain "induction dose" was not given properly, patients had a much weaker immune response to the vaccine.

"In that regard, vaccines are like drugs," he says. "The dose and timing have to be just right."

The immunological response to the tumor cell was important not only in determining if the melanoma grew back, but also affected the length of their survival after relapse. In fact, about 25 percent of the DTH (+) patients who relapsed were still alive after five years.

"That observation suggests that the vaccine changed the biology of the disease," says Berd. He believes that these findings should be applicable to other experimental cancer vaccines.

"Generally, in the vaccine field, people don't worry about the dose, how often they give it and the injection site," he says. "We show that these things matter. These parameters are important and people will need to figure them out if they want to get their vaccines to work."

Berd and his colleagues are now developing a second-generation vaccine. The new vaccine involves using an additional chemical to modify tumor cells, making them in theory even more visible to the immune system.

AVAX Technologies, Inc., of Kansas City, Mo. - which has exclusive rights to the Jefferson-based vaccine against malignant melanoma - sponsored the research.

University of Pennsylvania Breast Cancer Vaccine Study Supported by Unique "Progress for Patients" Grant from Avon and National Cancer Institute

Researchers at the Abramson Cancer Center of the University of Pennsylvania have begun a Phase I clinical trial to evaluate the effectiveness of a telomerase peptide as a possible vaccine against breast cancer. The study will measure potential tumor cell shrinkage in patients after an immune response has been triggered to an antigen - the telomerase peptide - found in more than 90 percent of breast cancer tumors.

The study is made possible through a unique $500,000 grant from the "Avon-NCI Progress for Patients" Awards program, a special private-public partnership between the Avon Foundation, Inc. and the National Cancer Institute (NCI) dedicated to accelerating early phase clinical research into promising therapies.

"This is the first clinical study to use a telomerase peptide as a possible vaccine against breast cancer," said lead researcher Robert Vonderheide, MD, DPhil, an assistant professor at the Leonard and Madlyn Abramson Family Cancer Research Institute at the University of Pennsylvania. "Our hope is that the immune response will kill the cancer and improve the health of patients."

Twenty-eight patients with metastatic breast cancer will be enrolled in the study, which is expected to last two years. Patients will be injected with one of three escalating doses of the telomerase antigen in combination with adjuvant therapies (granulocyte-macrophage colony stimulating factor, GM-CSF) over a period of seven months. The immune and tumor response to the telomerase-based vaccine will be monitored over the duration of the study and compared to a control response to an injection of cytomegalovirus peptide.

The results of an earlier feasibility study - also led by Vonderheide and published in the February 1 edition of the journal Clinical Cancer Research - showed immune responses with little toxicity in seven breast and prostate cancer patients after they were injected with small amounts of a similar telomerase peptide vaccine.

"One breast cancer patient in the earlier study showed temporary tumor regression, prompting us to accelerate research into the possibility of a vaccine," said trial principal investigator Susan Domchek, MD, a breast medical oncologist at the Abramson Cancer Center and assistant professor at Penn's School of Medicine.

Fox Chase Cancer Center "Tailors" Radiation Therapy To Help Reduce Erectile Dysfunction in Men Treated for Prostate Cancer

Impotence, or erectile dysfunction, is one of the most dreaded complications following surgery or radiation therapy for prostate cancer. In a new study at Fox Chase Cancer Center, radiation therapy is being "tailored" for some patients to determine if impotence can be avoided.

The study is for patients who chose a form of radiation therapy called IMRT. All of the patients in the study will receive the standard dose of radiation to the prostate, but for half of the men, the treatment will be specifically tailored to reduce the amount of radiation that is delivered to the erectile tissues surrounding the prostate.

"The erectile tissues lie very close to the prostate. There is evidence that delivering lower doses of radiation to the erectile tissues will lead to fewer incidences of erectile dysfunction," said Eric Horwitz, MD, the Fox Chase physician leading the study. "Our first priority in treating someone with prostate cancer is to offer the most likely treatment that will cure the disease. Our preliminary data demonstrates that we can achieve a cure even after lowering the dose of radiation to the erectile tissues."

A recent Fox Chase study showed that the radiation delivered to erectile tissues can be reduced by as much as 60 percent without compromising treatment outcome. Other studies show that the best cure rates are achieved when high doses of radiation are delivered directly to the prostate.

"IMRT is the only technology that allows physicians to arrange the radiation beams in such a way that we can reduce the radiation to the erectile tissues while boosting the dose to the prostate," Horwitz said.

IMRT is the latest of a series of technologic advances designed to improve the precision of radiation therapy. IMRT allows for the very precise delivery of radiation by dividing each beam into 60-100 multiple segments. This allows physicians to maximize the dose to the tumor where it is thickest and minimize the radiation dose to the surrounding healthy tissue, enabling the radiation oncologist to administer high doses of radiation with extreme precision to the targeted prostate while sparing surrounding healthy organs.

All patients in this clinical study will receive the same standard dose of radiation delivered to the prostate using IMRT. Some patients, however, will be randomly selected to receive the specially tailored treatment plan to reduce the level of radiation delivered to erectile tissues.

"IMRT provides excellent control over the radiation dose we deliver," said Horwitz. "Many places are offering patients only partial treatment using IMRT, but it is critical that patients receive IMRT from the start until the end of treatment in order to realize the full potential of this treatment."
Horwitz suggests that patients seeking IMRT ask the following questions:

Q: How long have your physicians been using IMRT and how many patients have been treated?

At Fox Chase and other comprehensive cancer centers, physicians have been using IMRT for almost 4 years. Fox Chase has treated more than 1,300 patients with IMRT.

Q: What technologies are employed to ensure daily accuracy when treating prostate cancer?

Since the prostate moves inside your body, it is important that it be identified daily so that treatment can be adjusted to reflect the prostate's movement. At Fox Chase, this is accomplished with MRI planning, daily BAT ultrasound, and the CT-on-Rails.

Q: Is there a physicist dedicated to working on the IMRT treatment plans?

At Fox Chase, we have a staff of physicists who design treatment plans daily.

Philadelphia International Medicine is an organization that provides medical and patient support services to international patients. It also provides continuing medical education and health care training and education to international physicians, administrators and other practitioners. As the international department of several Philadelphia-area hospitals, international patients gain access to physicians and hospitals rated among the best in the world through one telephone call to PIM. You can reach PIM by calling 1-215-735-3575; fax, 1-215-790-1267; or e-mail, physicians@philadelphiamedicine.com . You can find out more about PIM through its Website at www.philadelphiamedicine.com .