Hormonal Therapy

Early versus deferred androgen suppression in the treatment of advanced prostatic cancer: A systematic review

the Cochrane Library 2, 2005
T Wilt, B Nair, R MacDonald and J Rutks

Study purpose: Androgen suppression refers to treatments that use drugs to interrupt a man’s production of male hormones like testosterone that help prostate cancer cells grow. It is a mainstay of therapy for men with “advanced” prostate cancer that has spread outside the prostate gland. However, it remains unclear whether starting androgen suppression treatments as early as possible actually helps men when compared to the standard method of “deferred” androgen suppression, done at a later date when a man’s prostate cancer is worsening. This review judges the usefulness of both early and deferred androgen suppression.

Study description: The reviewers used computerized medical databases to find relevant published studies. Four different trials involving a total 2,167 men were chosen for study. Each of the studies had randomly divided its participants into groups getting either early androgen suppression treatment or later treatment.

Findings: The authors found that 88% of the men in the trials who got early androgen suppression were alive after one year. After two years, 73% remained alive, a percentage that dropped over five and ten years (44% and 18%, respectively). In comparison, men who received the later deferred therapy were worse off: the percent of their “overall survival” at one, two, five and ten years was 86%, 71%, 37%, and 12%. The authors calculated an overall estimate for the difference in time lived among all the participants in the studies, but this total overall survival rate was only statistically significant at ten years — in reality, few patients lived that long. Complications from the treatment were found in only one study, but happened more often in the early treatment group.

Conclusions: Early androgen suppression for treatment of advanced prostate cancer reduces the worsening of disease experienced by patients and limits complications due to worsening cancer.

Note: The authors note that results from the four studies were influenced by differences in study methods and design.

Meta-analysis of clinical trials of atrasentan 10 mg in metastatic hormone-refractory prostate cancer

Journal of Clinical Oncology

2004 ASCO Annual Meeting Proceedings 23(16S): 4563, supplement June 2005
N J Vogelzang, J B Nelson, C C Schulman, D P Dearnaley, F Saad, D J Sleep, J D Isaacson and M A Carducci

Study purpose: This meta-analysis compares and analyzes results from two studies where 1,002 men were given ten milligrams of the medication atrasentan to fight metastatic hormone–refractory prostate cancer or HRPC — cancer that spreads outside the prostate and is unresponsive to treatment blocking the male body’s production of the hormone testosterone, which feeds prostate cancer cells. Sold under the name Xinlay, atrasentan is an endolethin-A receptor antagonist that can halt prostate cancer cell growth and make cells more likely to die. Research from the two original studies suggests that 10 mg of atrasentan delays the worsening of cancer that has spread to bony sites in the body, and changes the way tumours and bone interface.

Study description: A meta-analysis is a statistical method combining results from studies in order to re-examine the overall evidence together. In this study, a meta-analysis was performed to more precisely define the benefit of atrasentan (10 mg) in HRPC patients. Results were put together from 1,002 men in two different studies that stopped observing patients when their cancer worsened. The authors of the meta-analysis re-examined the original data to observe the time it took for the cancer to worsen after taking atrasentan, the time before patients felt bone pain, and the time it took for serum prostate-specific antigen (PSA) tests to indicate the cancer was worsening.

Findings: Compared with taking a placebo, patients treated with atrasentan were 14% less likely to have a worsening of their cancer and 18% less likely to feel bone pain. They also had a 22% less chance of seeing PSA results worsen. The probability of not having their prostate cancer worsen was 10% greater 3 months into treatment, and 22% greater at 6 months.

Conclusions: Taking atrasentan significantly benefits men with metastatic HRPC.