Intermittent Taxotere/Calcitriol Chemotherapy Feasible in Treatment of Advanced Prostate Cancer

Treatment "holidays" may allow disease to be managed as chronic, rather then acute, condition

CHICAGO, Ill. /PSA Rising/ June 3. 2003 -- Advanced prostate cancer can be successfully treated with intermittent chemotherapy with no loss of disease control, according to a study conducted by Oregon Health & Science University scientists. The study was presented at the American Society of Clinical Oncology's annual meeting in Chicago, Ill.

Breaks -- or "holidays" -- in chemotherapy potentially allow prostate cancer to be managed as a chronic condition, rather than as an acute or life-threatening disease. Participants in a phase II study reported significant improvements in their quality of life as a result of chemotherapy holidays.

"Our data, while preliminary, suggest that intermittent chemotherapy is safe and that the cancer retains its sensitivity to treatment," said Tomasz M. Beer, M.D., an oncologist at the Oregon Health & Science University (OHSU) Cancer Institute in Portland, Ore., and lead investigator of the study.

Prostate cancer is the most common malignancy among men and the second leading cause of cancer death in men in the United States. Overall, roughly one in six American men will develop prostate cancer during his lifetime.

The optimal duration of chemotherapy treatment for patients with androgen-independent prostate cancer (AIPC) is unknown. In many studies of newer chemotherapy drugs, patients are treated until the disease progresses or until the side effects become intolerable. For patients who are responding to the chemotherapy, however, continuous treatment may be exposing them to unnecessary toxicity.

"Newer chemotherapy drugs are effective, but side effects accumulate when these drugs are used for prolonged periods of time. It is unrealistic to continue the treatment indefinitely," Beer said. "This study sought to answer the question: is it feasible to stop and start chemotherapy for patients who are responding well to the treatment?"

In the context of a phase II study of calcitriol plus docetaxel (Taxotere) for AIPC, Beer developed and tested an intermittent chemotherapy protocol. A primary criterion for inclusion in the study was a positive response to treatment measured by a prostate-specific antigen (PSA) of less than 4 ng/ml. PSA is a protein made only by prostate cells.

Certain prostate conditions, including prostate cancer, can cause high levels of PSA in the blood. PSA blood levels are monitored to help predict the presence and progression of prostate cancer. These patients were then given the option to select intermittent chemotherapy or to continue the existing treatment protocol. For patients electing chemotherapy holidays, the study protocol required resumption of treatment if a patient's PSA measurement rose by 50 percent or more and at least 1 ng/ml, or if other key indicators of disease progression were observed.

Of the 37 patients enrolled in the phase II study, 11 responded to chemotherapy to the degree necessary to meet criteria for inclusion in the study. Median treatment length for these men was 45 weeks. Eight of the 11 eligible men, ranging in age from 46 to 82, chose to suspend their chemotherapy. Of these eight men, the median length of the treatment holiday was 20 weeks with individual lengths ranging from 13 to 43 weeks. Chemotherapy treatment was resumed for seven patients, while one patient remains on the initial treatment holiday after 43 weeks. Of the seven patients who resumed chemotherapy treatment, three remain on an intermittent therapy protocol, mixing chemotherapy treatment with holidays. In all cases, PSA levels stabilized or dropped once chemotherapy resumed.

"Our data suggest that giving chemotherapy intermittently is safe because there was no loss of disease control in any of the patients," Beer said.

Analysis of quality of life data collected during the study revealed that the chemotherapy holiday was associated with improvement of fatigue as well as a trend toward improvement of shortness of breath, increased appetite and decreased diarrhea, although there was a slight worsening of pain reported by some study participants.

"Instead of treating patients continuously, we can reduce their exposure to chemotherapy to allow them to have a better quality of life," Beer said. "This study suggests that a follow-on clinical trial with more patients to further investigate intermittent chemotherapy for the treatment of AIPC is warranted."

Tomasz M. Beer , M.D., is an assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine, and a member of the OHSU Cancer Institute.

This trial was sponsored by Aventis Pharmaceuticals. Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. Visit www.aventis-us.com for more information about Aventis in the United States.

Source, Oregon Health and Science University (OHSU) Cancer Institute. This story edited for PSA Rising by J. Strax. Page updated Oct 25, 2003.

Results of Dr. Beer's trial have been published

Br J Cancer. 2003 Sep 15;89(6):968-70. Intermittent chemotherapy in metastatic androgen-independent prostate cancer.Beer TM, and team. Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University. Intermittent use of chemotherapy for androgen-independent prostate cancer (AIPC) instead of treatment until disease progression may reduce toxicity. We prospectively tested this approach in eight AIPC patients responding to calcitriol plus docetaxel who reached a serum prostate-specific antigen (PSA) /=50% and 1 ng ml(-1). The median duration of treatment holiday was 20 weeks (13-43+weeks) and all patients retained sensitivity to re-treatment. Chemotherapy holiday was associated with an improvement of fatigue (P=0.05). Intermittent chemotherapy for AIPC is feasible and deserves further study.

Other publications by Dr. Beer

About Taxotere (docetaxel), Calcitriol and other matters

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Clinical Trials for Prostate Cancer at OHSU

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