Editing Angiotensin-Il Receptor Blockers (ARB)



{{TreatmentInfo
|drug_name=Angiotensin-Il Receptor Blockers (ARB)
|category=Hormones and Cancer Therapy
|book_text=Angiotensin-II is a peptide hormone produced from angiotensin-I by the action of
angiotensin converting enzyme (ACE). The main effect of angiotensin-II is
vasoconstriction and a resulting increase in blood pressure. Therefore ACE inhibitors and
angiotensin-II receptor blockers are used as anti-hypertensive drugs, especially in heart
disease. More recently these drugs have been repurposed for use in cancer studies.

A retrospective study published in 2012 (328) examined the steroid-sparing effects of
angiotensin-II inhibitors, incuding ACE inhibitors and angiotensin-II receptor blockers
(ARBs). Of a total cohort of 87 newly diagnosed glioblastoma patients, 29 patients were
identified who were treated prior to radiation for high blood pressure. 18 of these were
treated with either ACE inhibitors (n=3) or angiotensin-II receptor blockers (n=15).
Although no survival benefit with angiotensin-II inhibitors was observed in this study, the
18 patients treated with an angiotensin-II inhibitor required half the steroid dose
compared to all other patients in the study (mean prednisolone dose of 29 mg per day
versus 60 mg per day), and this difference remained significant in multivariate analysis
(p=0.003).

A later retrospective study by the same group published in January 2016 (329) focused
specifically on the angiotensin-II receptor blocker class of drugs and their effects on
vasogenic edema in glioblastoma patients. In this study, 11 patients taking angiotensin-II
receptor blockers (ARBs) for hypertension were compared with 11 matched patients with
similar age, tumor size, and tumor location, but not taking medication for hypertension.
There was a significant 66% reduction in the FLAIR ratio in the patients taking ARBs
compared to the matched patients not taking ARBs. As FLAIR signal can represent either
tumor infiltration or vasogenic edema, the nature of the peri-tumoral FLAIR signal was
assessed with apparent diffusion coeffient (ADC) mapping. Nine evaluable patients taking
28

ARBs had a 34% reduction in ADC ratios compared to their matched controls not taking
ARBs, confirming the ability of this class of drugs to reduce peri-tumoral edema.

A 2015 study, also by the group in France, suggests angiotensin-II inhibitors (including
ACE inhibitors and ARBs) may also lead to superior survival outcomes (330). In this
study, 81 GBM patients were included. Seven of these patients were taking ACE inhibitors
and 19 were taking ARBs for hypertension. The 26 patients using angiotensin-II
inhibitors had increased progression-free and overall survival (8.7 and 16.7 months)
compared to the patients not taking these drugs (7.2 and 12.9 months). Use of
angiotensin-II inhibitors was a significant positive prognostic factor for both PFS and OS
in multivariate analysis.

A randomized phase 3 trial in France (NCT01805453) has recently completed
recruitment, and is testing the influence of losartan (an ARB) versus placebo on the
steroid dose required to control edema on the last day of radiotherapy. Another drug in
this class, telmisartan, has superior penetration into the central nervous system (331) and
may therefore be a better choice.

See Chapter 13 for a discussion of Angiotensin system inhibitors plus Avastin
}}