June 5, 2007 The number of tumor cells circulating in the bloodstream of patients with metastatic, hormone-resistant, prostate cancer can predict how they will do with chemotherapy, according to results of an international trial. The findings, if backed by larger studies, could have important implications for designing personalized treatments for this very dangerous type of prostate cancer, the researchers say.
The team of scientists -- including first author Jose Moreno, M.D., clinical associate professor of urology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and the Kimmel Cancer Center at Jefferson -- looked at circulating tumor cells (CTCs) in 240 men with metastatic prostate cancer that failed hormone-depletion therapy. They compared levels prior to chemotherapy and after two to five weeks of treatment. They found that those men with more than five tumor cells per blood sample had a worse prognosis than those who had fewer cells. One half of the patients with more than five CTCs lived at least 10 months, whereas half of the men with fewer tumor cells lived substantially longer -- 21 months.
Dr. Moreno presents the trial's findings June 4, 2007 at the annual meeting of the American Society of Clinical Oncology in Chicago.
The results of the 65-site trial also showed that those patients who underwent chemotherapy and whose CTC number went down fared better and had a more favorable prognosis. That is, the level of response to chemotherapy was reflected in the CTC level, notes Dr. Moreno. The numbers held up even after up to 20 weeks of treatment. "If chemotherapy doesn't reduce the CTC level, it's information that enables the physician to change the drug regimen or perhaps stop treatment," he says.
Dr. Moreno notes that the prostate specific antigen has been a powerful biomarker for cancer presence and a useful way to gauge treatment effectiveness for years, though it has some flaws. He thinks that the group's findings show that CTCs can be a stronger marker.
"The other exciting aspect is in looking at men with earlier stage prostate cancer," he says. "One in four men may have circulating tumor cells at an early stage of prostate cancer. If we can identify those patients, perhaps we can observe and not treat with radical surgery because their cancer is more dormant."
Huntington Valley, Pa.-based Immunicon Corporation's technology enabled researchers to visualize circulating tumor cells by using immunomagnetic beams that bind to the cell surface. It's been Food and Drug Administration-approved for clinical use in breast cancer.
Immunicon currently is working with several pharmaceutical companies in identifying targets on circulating tumor cells that are susceptible to various chemotherapy drugs, he explains. "Then doctors can select specific chemotherapy agents for specific patients," Dr. Moreno says. "The first immediate application is personalized medicine in advanced metastatic prostate cancer."
In addition, certain tests can be performed on CTCs, he notes. One future goal is to better characterize the tumor cells virulence.
Yet, one limitation is that "we didn't find as many circulating cells as we thought we would." In the study, circulating tumor cells weren't found in 38 percent of the men. "That might mean a better prognosis, but in fact their prognosis still isn't very good," he points out. "There are some limitations in our ability to detect them."
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