Renin-Angiotensin-System Inhibitors for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: OncoToxSRA, a Preliminary Cohort Study

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting adverse side effect of treatment. CIPN affects the oncological prognosis of patients, as well as their quality of life. To date, no specific pharmacological therapy has demonstrated effectiveness in preventing CIPN. Accumulating preclinical evidence suggests that renin-angiotensin system (RAS) inhibitors may have neuroprotective effects. One hundred and twenty patients were included in this observational study and were followed from the beginning of their neurotoxic chemotherapy schedule until their final assessment, at least one month after its cessation. The National Cancer Institute’s common toxicity criteria 4.0 (NCI-CTC 4.0) were used to grade the severity of adverse events. Follow-ups also included electrochemical skin conductance and scales for pain, quality of life and disability. Among patients receiving a platinum-based regimen, the mean grade of sensory neuropathy (NCI-CTC 4.0) was significantly lower in the RAS inhibitor group after the end of their anticancer treatment schedule. Because of the observational design of the study, patients in the RAS inhibitor group cumulated comorbidities at risk of developing CIPN. Randomized controlled trials in platinum-based regimens would be worth conducting in the future to confirm the neuroprotective potential of RAS inhibitors during chemotherapy.

Angiotensin-Related Peptides and Their Role in Pain Regulation

“…In addition to reducing a patient's quality of life, CIPN can suppress the efficacy of chemotherapy. Recently, a preliminary cohort study of patients on platinum-based regimens reported significantly less sensory neuropathy after chemotherapy in patients taking Ang-related drugs (AT1 receptor blockers or ACE inhibitors) compared with the control group [39], indicating that the neuroprotective effects of Ang-related drugs may be effective in CIPN. Additionally, continuous administration of losartan inhibited paclitaxel-induced mechanical hyperalgesia in rats by decreasing the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein (MCP)-1 in DRG [40].…”

The Role of Angiotensin Receptor Blockers in the Personalized Management of Diabetic Neuropathy

“…Neither valsartan nor lisinopril had any effect on baroreflex sensitivity [ 60 ]. A recent observational study also suggested that treatment with either ARBs or ACE-Is protects against platinum-induced sensory neuropathy [ 61 ]. These discrepant results are partly due to the small number of patients and differences in patients’ characteristics, duration of treatment, and index of autonomic function.…”

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

“…In the primary afferents including the dorsal root ganglion (DRG) and sciatic nerves, the Ang II/AT 1 receptor system may contribute to the development of neuropathic pain 5 . It is to be noted that clinical and preclinical studies have suggested the involvement of the Ang II/AT 1 receptor system in the chemotherapy-induced peripheral neuropathy 8 – 10 . Activation of AT 2 receptors expressed in macrophages is also implicated in neuropathic pain 11 , 12 , and the effectiveness of AT 2 receptor antagonists against neuropathic pain has been demonstrated in clinical and preclinical studies 13 – 15 .…”