UCSF includes prostate cancer patients with kidney and melanoma patients in "less toxic" stem cell trial
05-Oct-2000 /PSA Rising/- A new treatment for prostate cancer, kidney cancer and melanoma is being tried at UCSF Comprehensive Cancer Center. Patients can enroll now if a sibling whose immune system matches their own will act as a stem cell donor.
The aim of the clinical trials is to find out if early immune cells, called stem cells, can be collected and transferred from a patient's sibling into the patient to attack the cancer.
Using a similar treatment, investigators at the National Institutes of Health (NIH) recently demonstrated that this technique could be used to fight advanced kidney cancer. The tumors shrank in ten of the 19 patients in the NIH trial. Three of those patients had complete responses, with all evidence of cancer disappearing. The study was reported in the September issue of the New England Journal of Medicine.
Mark Frohlich, MD, and Peter Sayre, MD, PhD, both UCSF assistant professors of medicine, are co-investigators for the UCSF trials. They hope to confirm the NIH results in kidney cancer and determine if these donated stem cells can also be used to target prostate cancer and melanoma.
Frohlich and Sayre plan to enroll five to 10 patients in each of the trials. If they can demonstrate the treatment is safe and shows some evidence of tumor shrinkage -- or in the case of prostate cancer, lower levels of PSA, a protein in the blood that indicates cancer-- they will expand the trials to include additional patients.
"The principle behind the study is to replace the patient's immune system with that of his or her sibling," Frohlich said. "The hope is that the transplanted immune system will be able to attack the cancer in a way that the patient's own immune cells have been unable to do.
The donor's immune system must be compatible, or "matched" with the patient's. There is approximately a 25 percent chance that siblings will have matched immune systems, Frohlich said.
Stem cells are early blood cells that give rise to all the different blood cell types, including cells responsible for mounting an immune response. The transfer of another person's stem cells is called an "allogeneic" stem cell transplant.
This technique has been used for decades to treat leukemia, lymphoma and other blood cancers. Now it is being tested on solid cancers using a "much less toxic approach," the researchers say.
With leukemia and other blood cancers, stem cell transplantation is used to replenish the immune cells and other blood cells after patients are given high doses of chemotherapy, often combined with total body irradiation. This therapy works to kill the cancer residing in the bone marrow. As a byproduct of this intensive treatment, the normal bone marrow is irreparably damaged requiring that a new blood and immune system be infused into the patient. The patient's immune system is suppressed to enable the transferred cells to grow and multiply, or "engraft." The transferred stem cells repopulate the bone marrow with new blood cells that create a new immune system. Research has shown this new immune system often plays a key role in killing any residual cancer left in the bone marrow after the chemotherapy.
But side effects of standard allogeneic transplants are significant. Patients who undergo this procedure are typically hospitalized for weeks to months. Many patients die from complications of the transplant procedure, Frohlich said.
Recent research suggests that stem cells can engraft with much less toxic preparative regimens. In this newer approach, the goal is to allow the transferred immune system to deliver the anti-cancer effect, rather than the chemotherapy. In the UCSF trials, Frohlich and Sayre plan to deliver the treatment on an outpatient basis. Patients will be hospitalized only if complications arise.
The UCSF treatment plan:
The donor is given injections of a growth factor for five days to stimulate stem cells to spill out of the bone marrow and into the blood stream. The donor is connected intravenously to a machine that collects the blood cells and returns the remainder of the blood to the donor. Prior to transfer of these cells to the patient by infusion, the patient is treated with a low dose of total body irradiation and special medications to prevent his or her immune system from rejecting the transferred cells. The immunosuppressive medications are slowly tapered off over several months, and the patient's blood is tested periodically to determine if the donated cells have engrafted. Some patients will receive additional donor cells that have been frozen and stored if they need them.
There are still significant risks to these "low dose" stem cell transplants, Frohlich said. "While the hope is that the transferred cells will attack the cancer, they may also attack a patient's normal cells," he said. This condition, called "graft versus host disease" may cause skin rashes, fever, low blood counts and liver damage. In addition, suppressing the patient's immune system while waiting for the donated cells to engraft places the patient at risk of infection, and possibly cancer acceleration. In the NIH study, two of the 19 patients died of treatment related complications and it took approximately four months on average for patients to respond to the treatment.
The prostate cancer trial is paid for by CaP Cure, an organization that provides money for prostate cancer research. For more information on the kidney and prostate cancer studies, please call 415-885-7331. For the melanoma trial, please call 885-7546. C
The New England Journal of Medicine -- September 14, 2000 -- Vol. 343, No. 11(abstract, paid registration for full article) Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell Transplantation Richard Childs, Allen Chernoff, Nathalie Contentin, Erkut Bahceci, David Schrump, Susan Leitman, Elizabeth J. Read, John Tisdale, Cynthia Dunbar, W. Marston Linehan, Neal S. Young, A. John Barrett, Emmanuel Clave, Diane Epperson, Virginia Mayo
Cancer Immunotherapy with Alloreactive Lymphocytes, The New England Journal of Medicine (editorial) -- September 14, 2000 -- Vol. 343, No. 11
Related Web Sites
CaP CURE The Association for Cure of Cancer of the Prostate (site opens in a new window)
Physicians, Hospitals and Labs (PSA Rising resources list)
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