Now, a Jefferson radiation oncologist plans to use a grant from the Department of Defense to test the potential effectiveness of a new therapy aimed at thwarting the effects of the spreading disease.
"The strategy is to use bone-targeted agents upfront in combination with standard treatment – a combination of hormones and radiation – for high-risk prostate cancer," says Richard Valicenti, M.D., associate professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University and Jefferson's Kimmel Cancer Center in Philadelphia.
Many cases of prostate cancer are thought to be fed by male hormones known as androgens. One strategy against the disease, then, is to eliminate or limit androgen production. In addition, Dr. Valicenti explains that previous studies have shown evidence of an interaction between radiation and hormones, in effect, making the spreading cancer cells more sensitive to radiation. But the treatment has limited effectiveness.
Dr. Valicenti is developing a clinical trial to study individuals at increased risk for having prostate cancer spreading to the bones, but whose disease has not shown any outward clinical signs of having done so to date.
"We're hypothesizing that the same sort of combination [of hormones and radiation] could be used to treat microscopic bony metastasis," he says.
He and his co-workers are using an agent that is "preferentially taken up by the bone," he explains. The idea is that the agent, called samarium-153 ethylenediaminetramethylene phosphonic acid (EDTMP), or Quadramet – which consists of a "phosphonate" attached to a radioisotope that emits radiation – will attack cancer cells that have spread from the prostate to the bone. According to Dr. Valicenti, Quadramet – which is manufactured by Cytogen Corp. in Princeton, N.J. – "seems to primarily target prostate cancer sites that harbor bony metastases." It was previously used for pain reduction.
Dr. Valicenti currently is completing a phase I trial looking at the safety and feasibility of using the strategy of a bone-targeted treatment.
"The thinking is that this will help improve a reduction in death rates from prostate cancer," says Dr. Valicenti. In 2004, an estimated 29,000 men will die of prostate cancer, with complications from bony metastases a contributing cause in the majority of deaths. It is the second leading cause of cancer death in men.
The DOD award – one of seven initial proposals to be funded – is initially for $100,000 for one year to develop an infrastructure to carry out a two-to-three-year trial. When he and his co-workers show the DOD that they have developed the necessary plan to carry out a phase II trial, they will receive an additional $1 million from the government agency for three years to carry out the trial. They must submit a proposal for a clinical protocol by December. Only five will be funded. The trial, he expects, will be at several centers and involve approximately 60 or 70 patients. It could begin next year.