CALCIUM CHANNEL BLOCKERS ARE PROBABLY RADIOPROTECTIVE

May 15, 2012 (Barcelona, Spain) — Calcium channel blockers might have a radioprotective effect in patients undergoing radiotherapy for prostate cancer, according to research presented here at ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference.

Both during and after radiotherapy, calcium channel blockers used to treat hypertension had a protective effect against late rectal bleeding, reported Mariangela Massaccesi, MD, from radiotherapy unit at the Fondazione di Ricerca e Cura "Giovanni Paolo II" Universita Cattolica de S. Cuore in Camobasso, Italy.

"I think this is a very fluid field at the moment...because there is really quite strong evidence out there that this could have a major benefit," said the chair of the session, David Paul Dearnaley, MD, from the Institute of Cancer Research, Royal Marsden Hospital in Sutton, United Kingdom.

"In treating prostate cancer, there is a growing awareness that...we have to think about reducing side effects," he said in an interview with Medscape Medical News. "I think one has to be very cautious about overinterpreting [this study], but it's another piece of information that is pointing to the fact that there may be something in there that we should be exploring."

The researchers analyzed 278 patients with histologically proven prostate adenocarcinoma who underwent either 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy for prostate cancer, and who had a minimum of 6 months of follow-up.

The impact of potentially confounding variables, such as previous abdominal surgery, chronic pulmonary disease pelvic irradiation, radiotherapy technique, and dose and the use of angiotensin-converting-enzyme (ACE) inhibitors, beta blockers, and calcium channel blockers, on late radiation-induced rectal bleeding was assessed in univariate and multivariate analyses.

On univariate analysis, 2 variables — delivery of a radiation dose above 70 Gy and the use of ACE inhibitors — were associated with a higher incidence of late rectal bleeding. In contrast, compared with no use, the use of calcium channel blockers was associated with longer 3-year rectal-bleeding-free survival (89.9% vs 66.5%; P = .04).

On multivariate analysis, the use of calcium channel blockers remained significantly protective (hazard ratio [HR], 0.34), compared with the use of ACE inhibitors (HR, 1.47) or beta blockers (HR, 1.30).

A body mass index greater than 30 kg/m² was also protective (HR, 0.50), as was pelvic irradiation (HR, 0.66) and intensity-modulated radiotherapy (HR, 0.57).

Other factors associated with a higher risk of late rectal bleeding included a radiation dose higher than 70 Gy (HR, 3.02), chronic pulmonary disease (HR, 2.77), and previous abdominal surgery (HR, 1.19).

"There are 4 studies now that have shown that patients with hypertension have fewer side effects after radical radiotherapy than patients without hypertension," said Dr. Dearnaley, who has himself been involved in some of this work. "That is a slightly odd finding until one thinks laterally, and sees that perhaps it's not the hypertension and vascular damage that might be related, but actually the drugs that these patients are taking to treat the hypertension."

"There is now a lot of interest in trying to pin down what drugs, which are in very high use, might be related to this effect," he said.

Dr. Dearnaley explained that when he and his colleagues first identified this association (Clin Oncol [R Coll Radiol]. 2011;23:613-624), "we thought that it was a fluke.... But we went to the literature and found 3 large studies that had noticed the same effect; it was actually reported, but no comment was made about it." A fourth study showed no effect.

"We worked very closely with a gastroenterologist who became interested because he felt some of the mechanisms of antihypertensive drugs — and potentially statins — were of an anti-inflammatory nature and might affect the development of late side effects. He has since analyzed a group of patients with bowel side effects after the treatment of prostate and other cancers, and has found a very strong hint that the use of antihypertensives is protective."

Tackling adverse effects is an "absolutely critical issue," according to Dr. Dearnaley. "We have a whole range of treatments that are very effective; forms of prostatectomy, brachytherapy, radiotherapy — all of these treatments are effective. What really matters is that you don't damage patients in the long term, because 95% of these patients are going to be alive 10 years later," he said.

"At the moment, there is this idea that there may be some drugs out there that are very commonly used, that are safe, and that have been used in hundreds of thousands of patients, that may affect the production of radiation side effects. But we don't know which drugs, we don't know what dose, and we don't know when those drugs need to be given. There is a lot of investigation and detective work to be done here," Dr. Dearnaley said.

Dr. Massaccesi and Dr. Dearnaley have disclosed no relevant financial relationships.

ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference: Abstract PD-0118. Presented May 10, 2012.