HORMONE TREATMENTS BEFORE RADIATION NOW CONSIDERED EFFECTIVE
-Mouse Studies Quell Worries from Previous Prostate Cancer Study
Radiation oncologists have eagerly anticipated a follow-up to previous studies that implied radiation treatment for prostate cancer was less effective after the use of drugs to suppress hormones. Now, Johns Hopkins Kimmel Cancer Center scientists say their tests provide evidence that hormone therapy will not diminish the value of radiation.
The root of clinicians' concerns began five years ago when studies revealed that suppressing hormones in prostate tumors destroys tiny blood vessels that carry oxygen to cells within the tumor. But oxygen also plays a critical role in biochemical pathways that help radiation kill cancer cells by immobilizing their DNA repair process. If true, these oxygen-depleted tumors would be less likely to respond to radiation.
Theodore DeWeese, M.D., professor and chair of the Department of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins, led new tests in more than 50 rats whose prostates closely resemble human ones. "We used several rigorous tests, including a small fiberoptic probe and florescence, to detect oxygen levels in the prostate, and no rat showed any indication of low oxygen levels following hormone suppression," he says. It is still unclear as to how oxygen remains in the tumor without the small blood vessels, but DeWeese believes that clinicians can be assured that hormone therapy will not cause radiation to be less effective.
(Abstract #2399, Proceedings of the American Society for Therapeutic Radiation and Oncology, 2005)
LEUKEMIA DRUG SHOWS MODEST BENEFIT FOR PROSTATE CANCER
Johns Hopkins Kimmel Cancer Center researchers have found that the leukemia drug imatinib (Gleevec), which is being tested in various cancers including colon, ovarian and pancreas, may not work alone against prostate cancer. Previous studies have already found that imatinib is ineffective for metastatic prostate cancer. This new study shows only modest benefits in suppressing PSA levels for some men with localized prostate cancer. But, the researchers say that combining imatinib with other chemotherapy drugs may be something to study.
"Even though Imatinib was tolerable and easy to administer, using this drug alone was not enough to lower the majority of patients' PSA levels," says Theodore DeWeese, M.D., professor and chair of the Department of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins.
DeWeese's study is one of the first to evaluate imatinib in men with non-metastatic prostate cancer. All 24 patients had rising PSA levels -- a sign of relapse -- despite surgery to remove the prostate or radiation therapy to destroy it. PSA levels in six patients (22 percent) remained stable while receiving imatinib for one year, and two patients (7 percent) experienced a decline in PSA that was not statistically significant. The remaining patients' PSA levels increased while taking the drug. Other researchers at Hopkins are conducting studies on using the chemotherapy drug docetaxel in men with non-metastatic disease. DeWeese believes that results of this study may help determine if adding imatinib to chemotherapy is worth pursuing for these patients. He says, "With the combination strategy, we may be able to kill cancer cells by two different pathways."
(Abstract #2141, Proceedings of the American Society for Therapeutic Radiation and Oncology, 2005)
RADIATION TECHNIQUE CAN DESTROY VESSEL ABNORMALITY IN BRAIN
Malformed blood vessels in the brain that are larger than the size of a silver dollar were once thought incurable by radiation alone. After a 10-year study, Johns Hopkins Kimmel Cancer Center researchers found that precise radiation techniques can cure or shrink some of these abnormalities.
Arterio-venous malformations (AVMs) are a collection of blood vessels that do not contain the smaller capillaries, which bring oxygen and nutrients to brain tissue. Recently brought to mass attention by a character in the HBO television show "Six Feet Under," AVMs can lead to deadly stroke and neurological problems. Brain surgery can be risky, and cutting off the blood supply to the vessels via embolization does not cure the problem.
Daniele Rigamonte, M.D., professor at Johns Hopkins and senior author of the study, says that image-guided methods that very precisely deliver large doses of radiation therapy have helped to cure more large AVMs. "We are encouraged to find that sterotactic radiosurgery is a relatively safe method, and some large AVMs can be completely obliterated," he says.
AVMs were cured in three of 12 patients treated with stereotactic radiosurgery in the past 10 years with an average of three treatments per year. AVMs in the rest of the group were reduced by an average of 64 percent. Side effects included persistent headaches in two patients and a partial seizure in another patient.
Rigamonte says that his team will continue to follow these patients to determine how long it takes on average to cure the AVMs.
(Abstract #180, Proceedings of the American Society for Therapeutic Radiation and Oncology, 2005)
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