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This is important because the optimal duration of chemotherapy treatment for advanced prostate cancer is unknown. In many studies of newer chemotherapy drugs, patients are treated either for a fixed number of treatment cycles or until the disease progresses or until the side effects become intolerable. For patients who are responding to the chemotherapy, however, continuous chemotherapy may be exposing them to unnecessary toxicity.
"More than one-third of advanced prostate cancer patients complete their first round of chemotherapy with the disease in control," said Tomasz Beer, M.D., director of the prostate cancer program in the OHSU Cancer Institute. "Indefinite chemotherapy is not practical because toxicity and side effects accumulate, so we wanted to find out if a patient can take breaks -- or 'holidays' -- in chemotherapy and then be retreated with the same chemotherapy."
Beer and his colleagues found that when treatment was restarted after a chemotherapy holiday, roughly three-quarters of study subjects responded again or experienced stabilized prostate-specific androgen (PSA), a protein made only by prostate cells that is monitored to help predict the presence and progression of prostate cancer. The median duration of the first chemotherapy holiday was 16 weeks.
"This was a clinically meaningful break for most of the subjects," Beer said. Prostate cancer is the most common malignancy among men and the second leading cause of cancer death in men in the United States. One in six American men will develop prostate cancer during his lifetime.
Beer will present initial results on intermittent chemotherapy for metastatic prostate cancer from the AIPC Study of Calcitriol Enhancing Taxotere (ASCENT) on Sunday, June 4, at the 2006 annual meeting of the American Society for Clinical Oncology.
ASCENT is a randomized, double-blinded, placebo-controlled clinical trial to evaluate an innovative formulation of high dose vitamin D (DN-101) given with docetaxel (Taxotere) for advanced prostate cancer research subjects who are no longer responding to hormonal therapy, a condition known as androgen-independent prostate cancer (AIPC). Two hundred fifty subjects participated in the study at 48 sites between September 2002 and January 2004.
DN-101 is a capsule that works by producing much higher blood levels of calcitriol than the body can produce from dietary vitamin D or vitamin D supplements. In high doses, it enhances many commonly used chemotherapeutic agents.
ASCENT subjects were eligible for holidays if they had a 50 percent PSA reduction that was tested and confirmed four weeks later, a PSA below 4 ng/ml and no other evidence of disease progression.
"About 18 percent of the ASCENT study population was eligible for a holiday," Beer said.
Researchers tested a protocol that included a PSA and clinical examination every four weeks and, for those with measurable disease, an assessment every eight weeks. Chemotherapy resumed after a confirmed PSA increase of 50 percent when the PSA was 2 ng/ml or more or for any other evidence of disease progression.
More than half the subjects responded with a greater than 50 percent PSA reduction when treatment was restarted after the holiday. Approximately one-quarter had stable PSA for at least 12 weeks and one-quarter percent progressed on therapy.
"These results are encouraging," Beer said. "Additional study is needed to more definitively determine the contribution of intermittent chemotherapy to the overall efficacy and toxicity of treatment."
Beer, an inventor of DN-101, and OHSU have a significant financial interest in Novacea, the manufacturer of DN-101. Novacea may have a commercial interest in the results of this research and technology. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee, and the Integrity Program Oversight Council was implemented.
Particulars:
ASCO Abstract No. 4518: Intermittent Chemotherapy in Metastatic Androgen-Independent Prostate Cancer (AIPC): Initial results from ASCENT
This study was funded by Novacea with support from Sanofi Aventis.