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PHILADELPHIA INTERNATIONAL MEDICINE® NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
For immediate release:
In this month's issue:
1. Trial at Jefferson Shows New Drug May Help Cancer Patients in Need of
Stem Cell Transplants
2. Penn Surgeons Use Completely Robotic Surgery To Treat Prostate Cancer
3. Fox Chase Researchers, Others, Say They Have Identified a Biomarker That
Indicates a More Aggressive Form of Prostate Cancer
Editors note: Research by Philadelphia International Medicine physicians may lead to new ways to treat some of our most challenging diseases. Below are some examples from our hospitals.
Trial at Jefferson Shows New Drug May Help Cancer Patients in Need of Stem
Cell Transplants
Philadelphia –A new drug may help cancer patients mobilize the cells necessary to restore their blood-forming system after high-dose chemotherapy, according to results from a clinical trial at the Kimmel Cancer Center at Thomas Jefferson University Hospital in Philadelphia and at other centers across the nation.
In the phase II trial, researchers were attempting to determine if patients with multiple myeloma or non-Hodgkin’s lymphoma who received the drug AMD-3100 along with the standard drug G-CSF (granulocyte-colony stimulating factor) would have more stem cells available for transplantation.
AMD-3100 blocks a specific cellular receptor, triggering the movement of stem cells out of the bone marrow and into the circulating blood, boosting the supply of marrow stem cells available for transplantation. Stem cell transplantation entails collecting certain types of cells known as hematopoietic stem cells from patients who receive treatment with high-dose radiation and/or chemotherapy for cancers such as leukemias, lymphomas and multiple myeloma, all of which involve the blood and immune system. The cells, once returned to the body, help restore the blood-forming system within the bone marrow – and the body’s immune system, which is severely damaged if not destroyed by treatment.
Stem cell transplantation is considered “front-line therapy for multiple myeloma, or cancer of the bone marrow, and for high-risk leukemia and lymphoma patients,” says Neal Flomenberg, MD, professor of medicine and director of medical oncology at Jefferson Medical College of Thomas Jefferson University, who led the trial at Jefferson.
The researchers found that all of the 25 patients (10 patients with multiple myeloma and 15 patients with non-Hodgkin’s lymphoma) given the drug combination could move enough cells from the marrow to the bloodstream compared to only 64 percent of those who had G-CSF alone. They report their results September 1, 2005 in the journal Blood.
As a result, Dr. Flomenberg says, there were fewer stem cell collections necessary and more stem cells retrieved. The greater the number of available stem cells, the more likely transplantation will be successful. In some cases, this can mean the difference between a patient being able to receive a transplant or not. The drug has little toxicity.
“One of the most important results from the trial was that nine patients who would not have been able to mobilize stem cells to go to transplant with G-CSF alone could now mobilize them with the combination of G-CSF and AMD-3100,” Dr. Flomenberg says.
In addition, some patients who received AMD-3100 needed fewer stem cell collections to get the necessary number of cells, making the overall process less taxing. Those who still required the same number of collections had a higher total of stem cells.
“It’s hoped that the drug combination will make white cell and platelet recovery quicker and allow patients who wouldn’t have otherwise been able to mobilize stem cells for transplant now be able to do so,” he says. Without adequate numbers of stem cells for transplantation, patients may have a delayed recovery of their immune systems and be at greater risk of infection.
Most patients undergo standard chemotherapy for four to eight months before
they have a stem cell transplant, he explains. Some patients won’t have a
transplant until their disease relapses and treatment once again puts them back
in remission. These treatments sometimes make subsequent stem cell collection
difficult.
Approximately 25 percent to 35 percent of transplant patients – and perhaps as
many as 65 percent – have trouble moving optimal numbers of stem cells from
their bone marrow into the bloodstream using G-CSF. “Some patients with the
standard approach don’t mobilize well, meaning more collections and often a poor
or unusable cell product,” he says.
Dr. Flomenberg believes that the drug combination will become a standard treatment for such cases involving stem cell transplantation. “The treatment has potential to alter the standard of practice,” he says.
Researchers currently are conducting two phase III trials comparing G-CSF and placebo to G-CSF and AMD-3100 in 600 patients with either non-Hodgkin’s lymphoma or multiple myeloma, he notes. Jefferson is participating in both trials, in addition to another phase II trial with AMD-3100 alone.
The research is sponsored by AnorMED Inc., a Vancouver, British Columbia-based drug development company. AnorMED’s efforts are aimed at the discovery and development of small molecule therapeutics to treat diseases including HIV, rheumatoid arthritis, asthma and cancer.
Penn Surgeons Use Completely Robotic Surgery To Treat Prostate Cancer
Prostate cancer is the second leading cause of death among American men. It is estimated that one in six males will develop the disease during his lifetime. However, promising new treatment options have been developed to help combat this threatening disease.
One of the most innovative of these treatments is robotic-assisted laparoscopic prostatectomy (removal of the prostate). The University of Pennsylvania Health System is currently one of only a handful of facilities across the country offering this minimally invasive, high-tech treatment. David I. Lee, MD, a national expert in robotic surgery, was recruited to Penn and named Chief of the Division of Urology at Penn Presbyterian Medical Center, where the robotic prostate program is based.
Many factors make robotics an exceptionally valuable tool in the operating room during prostate surgery, for both the patient and surgeon. “Perhaps two of the most-feared possible long-term effects of a radical prostatectomy are erectile dysfunction and urinary incontinence,” says Dr. Lee. “My specially-trained team and I have discovered that by using the robotic technique there is greater nerve sparing, which provides patients with the best chance for maintaining potency and continence.”
Robotic technology offers a number of advantages during surgery. For instance, the robotic “arms” filter even minute tremors of the human hand so to provide steadiness. The robot’s camera also provides a three-dimensional, stereoscopic image of the body’s interior, as opposed to a two-dimensional image on a flat screen. This improved perspective enables depth perception sharpens the visualization of the prostate and the network of nerves and tissue surrounding it.
Additionally, by scaling down the motion of the robotic instruments, the surgeon can perform extremely precise, intricate movements during the procedure. For example, if the surgeon’s hand moves five centimeters, he/she can scale the robotic hand to move only one centimeter.
Robotic technology also offers a number of advantages after surgery. Because laparoscopic surgery is minimally invasive and no large incisions are involved, robotic-assisted surgery provides numerous benefits for prostate cancer patients, including: less pain and scarring, diminished blood loss, a shorter hospital stay and reduced recovery period for a quicker return to daily activities.
The actual robot consists of a tower that manipulates instruments controlled from a console that is situated a few feet from the patient. At the console, the surgeon operates four robotic “arms” and “wrists” using hand and foot controls. One of the robotic arms holds a tiny video camera, one works as a retractor and the other two replicate the surgeon’s exact hand movements. The camera and instruments are inserted through small keyhole incisions in the patient’s abdomen. The surgeon then directs the robotic instruments to dissect the prostate gland and surrounding tissue.
Unlike standard laparoscopic approaches that require counter-intuitive movements by surgeons (whereby the surgeon must move his hand to the left in order to move the mechanical device to the right), the robotic technology affords surgeons the direct, “intuitive” control they exercise in traditional open surgical procedures, seamlessly translating their natural hand, wrist and finger movements at the console into corresponding micro-movements of laparoscopic surgical instruments inside the patient’s body.
Penn has been using fully robotic surgery for cardiac patients for the past three years and is currently studying its use for head and neck cancer surgeries. “The robotic prostate program is a continuation of Penn’s commitment to finding and applying the most precise, most beneficial surgical techniques to put patients on a quicker road to recovery with better outcomes,” said Dr. Lee.
Fox Chase Researchers, Others, Say They Have Identified a Biomarker That
Indicates a More Aggressive Form of Prostate Cancer
Fox Chase Cancer Center’s Chairman of Radiation Oncology, Alan Pollack, MD, PhD, presented the findings at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology of new biomarkers that indicate more virulent forms of prostate cancer.
“Staging factors for prostate cancer such as PSA and the Gleason score are extremely useful in predicting prostate cancer outcome,” explained Pollack. “However, new biomarkers hold promise in strengthening our ability to predict response to treatment. By identifying the more virulent forms of prostate cancer, we may be able to tailor treatment or develop therapies to target the abnormalities identified.”
In the Radiation Therapy Oncology Group-sponsored study (RTOG 92-02), Pollack and his colleagues show that the overexpression of a protein called MDM2 is a strong and independent predictor that the prostate cancer will metastasize beyond the prostate gland and indicates an increased chance of death from the disease.
The study involved 469 men treated with radiation and short- and long-term androgen deprivation therapy. The median follow-up was 70.5 months. An immunohistochemical analysis was conducted on prostate tissue to determine the amount of MDM2 in the prostate cancer cells.
While other biomarkers were associated with biochemical failure, distant metastasis or overall mortality, MDM2 was consistently associated with all three outcomes. MDM2 was associated with a doubling of distant metastasis (10 to 20 percent) and a nearly 10 percent reduction in five-year survival.
In addition to Pollack, other authors of the study include Michelle DeSilvio,
American College Of Radiology, Philadelphia, Pa.; Li-Yan Khor, Tahseen Al-Saleem
and Gerald E. Hanks (retired), all of Fox Chase Cancer Center; M. Elizabeth
Hammond, University of Utah School of Medicine, Salt Lake City; David Grignon
and Mingxin Che, Wayne State, Detroit, Mich.; Marvin Rotman, SUNY, Brooklyn, NY;
Varagur Venkatesan, University Western Ontario, London, ON, Canada; Roger Byardt,
Medical College of Wisconsin, Milwaukee, Wisc.; and Howard Sandler, University
of Michigan Medical Center, Ann Arbor.
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