Angiotensin-II Receptor Blockers (ARB)
| Property | Information |
|---|---|
| Drug Name | Angiotensin-II Receptor Blockers (ARB) |
| Overview | Angiotensin-II Receptor Blockers (ARBs), initially approved for hypertension, are being investigated for their potential to reduce vasogenic edema and steroid requirements in glioblastoma patients, showing promising effects in retrospective studies despite no direct survival benefits reported. Ongoing research, including a randomized phase 3 trial, aims to further explore the supportive role of ARBs in glioblastoma management. |
| FDA Approval | Yes (for hypertension; repurposed for cancer studies) |
| Used for | Investigational use in glioblastoma for potential reduction of vasogenic edema and steroid-sparing effects |
| Clinical Trial Phase | Retrospective Studies |
| Clinical Trial Explanation | Not specified |
| Common Side Effects | Varies by specific ARB; can include dizziness, hypotension, and renal function alteration |
| OS without | Not specified |
| OS with | Not specified; studies have focused on steroid requirements and edema control |
| PFS without | Not specified |
| PFS with | Not specified; primary focus has been on edema reduction and potentially improved quality of life |
| Usefulness Rating | 3 |
| Usefulness Explanation | Not specified |
| Toxicity Level | 2 |
| Toxicity Explanation | Angiotensin-II Receptor Blockers, primarily used for high blood pressure, have been repurposed for cancer studies, specifically for reducing swelling around brain tumors and lowering the need for steroids. Common side effects can include dizziness, low blood pressure, and alterations in kidney function. However, these are generally mild and manageable, hence the relatively low toxicity rating. While these drugs have shown potential in improving some symptoms, their impact on tumor growth or survival rate is still under investigation. |
Notes: ARBs, primarily used for hypertension, have shown potential in reducing steroid dose requirements and peri-tumoral edema in glioblastoma patients in retrospective studies. While no direct survival benefit has been observed, the reduction in steroid dosage and control of edema suggest a potential supportive role in glioblastoma management. Further research, including a randomized phase 3 trial in France, is exploring the impact of ARBs like losartan on glioblastoma treatment outcomes.
From Ben Williams Book: 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 AvastinProperty "Has original text" (as page type) with input value "Angiotensin-II is a peptide hormone produced from angiotensin-I by the action of</br>angiotensin converting enzyme (ACE). The main effect of angiotensin-II is</br>vasoconstriction and a resulting increase in blood pressure. Therefore ACE inhibitors and</br>angiotensin-II receptor blockers are used as anti-hypertensive drugs, especially in heart</br>disease. More recently these drugs have been repurposed for use in cancer studies.</br></br>A retrospective study published in 2012 (328) examined the steroid-sparing effects of</br>angiotensin-II inhibitors, incuding ACE inhibitors and angiotensin-II receptor blockers</br>(ARBs). Of a total cohort of 87 newly diagnosed glioblastoma patients, 29 patients were</br>identified who were treated prior to radiation for high blood pressure. 18 of these were</br>treated with either ACE inhibitors (n=3) or angiotensin-II receptor blockers (n=15).</br>Although no survival benefit with angiotensin-II inhibitors was observed in this study, the</br>18 patients treated with an angiotensin-II inhibitor required half the steroid dose</br>compared to all other patients in the study (mean prednisolone dose of 29 mg per day</br>versus 60 mg per day), and this difference remained significant in multivariate analysis</br>(p=0.003).</br></br>A later retrospective study by the same group published in January 2016 (329) focused</br>specifically on the angiotensin-II receptor blocker class of drugs and their effects on</br>vasogenic edema in glioblastoma patients. In this study, 11 patients taking angiotensin-II</br>receptor blockers (ARBs) for hypertension were compared with 11 matched patients with</br>similar age, tumor size, and tumor location, but not taking medication for hypertension.</br>There was a significant 66% reduction in the FLAIR ratio in the patients taking ARBs</br>compared to the matched patients not taking ARBs. As FLAIR signal can represent either</br>tumor infiltration or vasogenic edema, the nature of the peri-tumoral FLAIR signal was</br>assessed with apparent diffusion coeffient (ADC) mapping. Nine evaluable patients taking</br>28</br></br>ARBs had a 34% reduction in ADC ratios compared to their matched controls not taking</br>ARBs, confirming the ability of this class of drugs to reduce peri-tumoral edema.</br></br>A 2015 study, also by the group in France, suggests angiotensin-II inhibitors (including</br>ACE inhibitors and ARBs) may also lead to superior survival outcomes (330). In this</br>study, 81 GBM patients were included. Seven of these patients were taking ACE inhibitors</br>and 19 were taking ARBs for hypertension. The 26 patients using angiotensin-II</br>inhibitors had increased progression-free and overall survival (8.7 and 16.7 months)</br>compared to the patients not taking these drugs (7.2 and 12.9 months). Use of</br>angiotensin-II inhibitors was a significant positive prognostic factor for both PFS and OS</br>in multivariate analysis.</br></br>A randomized phase 3 trial in France (NCT01805453) has recently completed</br>recruitment, and is testing the influence of losartan (an ARB) versus placebo on the</br>steroid dose required to control edema on the last day of radiotherapy. Another drug in</br>this class, telmisartan, has superior penetration into the central nervous system (331) and</br>may therefore be a better choice.</br></br>See Chapter 13 for a discussion of Angiotensin system inhibitors plus Avastin" contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
