Zosia Chustecka

September 24, 2009

September 24, 2009 (Berlin, Germany) — The risk for heart disease is increased with all hormonal therapies used as primary treatment for prostate cancer, but the risk is increased more by gonadotrophin-releasing hormone (GnRH) agonist therapy than by antiandrogens. These results come from a huge new Swedish study, which also showed that the risk is increased for all types of cardiovascular disease, including ischemic heart disease, myocardial infarction, heart failure, and cardiac arrhythmias.

The findings were presented here at a presidential session at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress, and highlighted at a congress press briefing.

The finding that the risk for cardiovascular disease is increased across the board is "very relevant to daily clinical practice," said Fortunato Ciardiello, MD, from the Cattedra di Oncologia Medica at Naples University in Italy, who moderated the press briefing. "When we prescribe these drugs, we have to explain to our patients that this testosterone deprivation can affect other aspects of their lives."

"It is important to take heart disease into account before starting endocrine treatment, especially as these drugs are prescribed not only for metastatic prostate cancer but also for less severe disease," said presenter Mieke van Hemelrijck, a PhD student and cancer epidemiologist at King's College in London, United Kingdom.

Largest Study to Date; Focus on Primary Treatment

Although there have been reports of an increased risk for heart disease, mainly from the United States, overall the previous findings have been inconsistent, Ms. van Hemelrijck explained to Medscape Oncology.

"This is the largest and most comprehensive study to date," she said. It is also the first to show a difference in risk between the different types of hormonal therapies, and to examine the effect on different types of cardiovascular disease, she added.

The researchers analysed data from the Swedish National Prostate Cancer Registry, which includes data on more than 80,000 men, accounting for more than 96% of all cases of prostate cancer in Sweden. They found 30,642 men who had received hormonal therapy as the primary treatment for their prostate cancer between 1997 and 2006.

About 10% of these men received antiandrogens, 30% received GnRH agonists, and 38% received a combination of the 2 therapies, Ms. van Hemelrijck told Medscape Oncology. In addition, some men underwent orchidectomy. They were followed for an average of 3 years.

The team compared national statistics for hospitalization and mortality for these men with those in the general population, taking into account age and history of heart disease.

"We found that prostate cancer patients treated with hormone therapy had an elevated risk of developing all of the individual types of heart problems, and that they were more likely than normal to die from those causes," Ms. Van Hemelrijck reported.

The increase in risk was seen within a few months of initiating hormone therapy, she added.

Compared with the general population, men taking hormonal therapy for prostate cancer showed an increased risk of developing cardiovascular disease that required hospitalization, and of dying from this. Specifically, their risk was increased:

  • by 24% for a nonfatal myocardial infarction and by 28% for a fatal myocardial infarction

  • by 19% for developing cardiac arrhythmias and by 5% for dying from this

  • by 31% for developing ischemic heart disease and by 21% for dying from this

  • by 26% for heart failure (for both incidence and mortality).

About 10 extra ischemic heart disease events a year will appear for every 1000 prostate cancer patients treated with such drugs.

"If we have observed a causative effect, then for all hormone therapies put together, we estimate that, compared with what is normal in the general population, about 10 extra ischemic heart disease events a year will appear for every 1000 prostate cancer patients treated with such drugs," Ms. van Hemelrijck noted.

However, the therapies differed from one another in the amount by which they increased the risk for cardiovascular disease.

Differences Between Hormonal Treatments

Patients who were taking GnRH agonist therapy were at the highest risk, and those taking antiandrogens alone were at the lowest risk, although the risk was still elevated in these patients for all of the cardiovascular problems except for death from ischemic heart disease, Ms. Van Hemelrijck explained.

For example, the risk for heart failure was increased by 5% with antiandrogens and by 34% with GnRH agonists, and the risk for ischemic heart disease was increased by 13% with antiandrogens and 30% with GnRH agonists.

The increase in risk seen in men who had undergone orchidectomy was similar to the increase in those treated with GnRH agonists. Both approaches dramatically reduce the amount of circulating testosterone; however, antiandrogens do not reduce the amount of testosterone in the body, they inhibit it from reaching the prostate cells, the researcher explained.

"The finding that antiandrogens carry the least heart risk supports the view that circulating testosterone may protect the heart," she noted.

In addition, the increase in the risk for cardiovascular disease seen with hormonal therapy for prostate cancer was less pronounced in men who had a history of such problems. For instance, men who had a history of ischemic heart disease had a 17% increased risk of developing a new event, compared with an increase of 41% in men with no history. The explanation might be that the men with a history of heart disease were already taking medication, which protected them from the further risk imposed by the hormone treatment, Ms. Van Hemelrijck suggested.

"We now need studies verifying the association and exploring plausible biological mechanisms," she said.

In the meantime, the main message from this study for doctors who prescribe hormonal therapies for prostate cancer is to be aware that they might increase the risk for cardiovascular disease, to take this into account when considering all potential treatment options, and to "be on the look out for it" in men taking these therapies, she said.

The study was funded by the Swedish Research Council, the Stockholm Cancer Society, and Cancer Research UK.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 0272. Presented September 22, 2009.

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