Testosterone can be the key to manhood, but it also stirs the growth of cancer cells in the prostate . So, injections of the hormone may seem like the last thing a man with such needs in cancer. But a new study shows that the shots can slow the progression of tumors untreatable prostate in some patients.
Researchers have known since the 1940s that reducing the levels of testosterone and other male sex hormones may curb prostate tumors. Today, a common treatment for prostate cancers that have spread to other parts of the body is chemical castration, drugs that reduce the body's production of testosterone and related hormones. But cancer cells generally adapt to low hormone levels and resume growth. For example, they sometimes handle more receptor molecules stimulated by testosterone or upgrade to a version of the receptor that does not need testosterone to encourage growth. Although researchers have developed new treatments to counter this resistance, such as drugs that block the receptor for testosterone, tumors often develop resistance quickly too.
The studies of cancer cells in a dish and tumors in animals have revealed a paradox of the so-called prostate cancer resistant to castration. Cancer cells that thrive when testosterone is rarely often die when exposed to high levels of the hormone. The experiments suggest that additional hormone disrupts DNA replication and results in fractures of the DNA, which can be fatal to a cell. This paradoxical relationship means that doses of testosterone may be beneficial against resistant tumors.
medical oncologist Michael Schweizer, now at the University of Washington, Seattle, and colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, tested this strategy in 16 men whose prostate cancers had become resistant to chemical castration. Most of their tumors had spread, or metastasized. In the study, the men continued to receive treatment for chemical castration, but every 28 days, the researchers also have their testosterone injection. Each sharp shooting blood testosterone levels well above normal, but gradually declined until they were close to the level produced by chemical castration. The justification for these oscillations, Schweizer says, is that "you do not let the cancer cells of the prostate to get used to a testosterone environment." The peaks of hormones will kill cancer cells that have adapted to low testosterone, while the valleys will smother the cells that need testosterone to grow.
to assess the progress made by the subjects, the researchers measured the amounts of specific antigen prostate (PSA) in the blood, an indicator of the growth of prostate cancer. Two patients left the study after the first round of treatment because of side effects. In seven of the remaining subjects, PSA levels increased during the first three cycles of treatment, suggesting that they do not receive the injections. But PSA levels dipped in seven others, a sign that their tumors may be decreasing. "The fact that half the guys who got through three cycles [of treatment] showed a response is encouraging," said Schweizer.
He and his colleagues performed CT scans on 10 patients to check the size of their metastasis, or tumor colonies generated by the initial growth. in four patients, metastases had decreased, and in one patient, they had disappeared, reports the online team today Science Translational Medicine . the five men were in the group that showed PSA decreases.
over time, however, the benefits of testosterone injections decreased. PSA levels started to increase after about 7 months, suggesting renewed growth in tumors. But even a short-term response could prolong patients' lives, because prostate cancer resistant to chemical castration is usually incurable, Schweizer notes. Although some previous studies have attempted to assess the effects on prostate cancer to boost testosterone levels, they do not provide the high doses of hormone required to kill resistant cancer cells, he said. Thus, the new work "is a first step towards finding out who will benefit from this treatment."
For patients who remained in the study, treatment side effects included nausea and hair loss, and the two subjects developed blood clots in the lungs. Of the two people who left the test early, we fell ill with pneumonia and died of sepsis, inflammation of body-wide infections that often results. This is not a typical consequence of testosterone therapy, Schweizer said, so the researchers believe it was caused by a chemotherapy drug that the patients also took over part of the study.
Some researchers and doctors feared that the testosterone treatment may accelerate tumor growth, says Charles Ryan, cancer endocrinology researcher and physician at the University of California, San Francisco, who has not participated. But the study shows that "there is potentially a large number of patients for whom this treatment is not harmful, but may be beneficial." However, he is not ready to change the way it treats cancer patients prostate until researchers conduct studies that confirm the effects of testosterone and clarify the risks of treatment.
"They intriguing clinical data," says medical oncologist and cancer researcher prostate Christopher Logothetis from the University of Texas MD Anderson cancer Center in Houston, who also was not connected to the study. But he was disappointed that the team did not test the biopsy samples of subjects to determine how testosterone influenced tumors. This analysis is essential for researchers to understand how to predict which patients will benefit from treatment and which might be harmed, he said.
Two other studies of testosterone therapy in patients with prostate cancer resistant to castration began, Schweizer notes, so that researchers may soon have a better idea of whether the treatment is superior to current approaches.
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