OPERA supplement for chemotherapy-induced peripheral neuropathy

This paper is part ofNMJ's Oncology Special Edition 2017. Read the newspaper or download the full edition here.

Relation

Desideri I, Francolini G, Becherini C, et al. Use of alpha-lipoic acid, methylsulfonylmethane and bromelain as dietary supplements (OPERA®) for the management of chemotherapy-induced peripheral neuropathy, a prospective study.Med. Onc. 2017;34(3):46.

Objective

To determine the efficacy and safety of OPERA® supplementation (240 mg alpha-lipoic acid, 40 mg Boswellia serrata, 20 mg bromelain, and 200 mg methylsulfonylmethane [MSM]) in a series of patients with chemotherapy-induced peripheral neuropathy (CIPN).

Draft

Prospective intervention study

Participant

Twenty-five Caucasian adults with CIPN during or after chemotherapy with potentially neurotoxic agents; Patients were included in the study at the first clinical manifestation of neuropathy. The diagnosis of CIPN was based on the National Cancer Institute-Common Toxicity Criteria for Adverse Event (NCI-CTCAE) v4.0 grade of ≥1 for sensory neuropathy, with at least one report of paresthesia of the fingers or toes (a criterion for grade 1).

Inclusion criteria were as follows: 18 years or older; Karnofsky performance score >70; Treatment with any of the following active substances: paclitaxel, docetaxel, nab-paclitaxel, oxaplatin, cisplatin, carboplatin, vinorelbine, vincristine, etoposide, eribulin mesylate; CIPN that developed after or during standard chemotherapy. Twenty-three patients (92%) were receiving chemotherapy with a neurotoxic agent at admission, while 2 patients (8%) had completed chemotherapy with a neurotoxic agent.

intervention

All patients were required to take one OPERA® capsule once daily, regardless of food intake.

Study parameters assessed

Chemotherapy-induced peripheral neuropathy was assessed at the enrollment visit and repeated every 3 weeks to 12 weeks using: National Cancer Institute-Common Toxicity Criteria (NCI-CTC) v3.0, sensory and motor neuropathy score; the clinical version of the Total Neuropathy Score (TNSc); and the total sensory score (mISS) of the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group. The Visual Analog Scale (VAS) for pain was used to assess pain intensity.

Primary outcome measures

The primary endpoint was the assessment of changes in measured values ​​after 12 weeks of therapy compared to baseline assessment. Secondary endpoints were assessment of reduction in neuropathy 12 weeks after initiation of therapy with OPERA®.

Key insights

The dietary supplement OPERA® was able to improve CIPN symptoms in a prospective case series of patients treated with neurotoxic chemotherapy without significant toxicity or interaction. In addition, no worsening of pain or CIPN symptoms has been reported with the use of OPERA®. No statistical analysis was performed for this study.

Practice implications

Chemotherapy-induced peripheral neuropathy describes damage to the peripheral nervous system that occurs in a patient who has received a neurotoxic chemotherapy drug. This is a common dose-limiting side effect in cancer patients treated with platinum-derived compounds, vinca alkaloids, taxanes and the proteasome inhibitors.¹The incidence of neurotoxicity varies depending on the agent used and cumulative dose, with rates ranging from 19% to greater than 85% in patients treated with multiple agents.²A recent meta-analysis showed a CIPN prevalence of 68.1% (95% CI: 57.7-78.4) within the first month after chemotherapy, 60.0% at 3 months, and 30.0% at 6 months or later.³

No reliably effective treatment to prevent or treat CIPN symptoms has been established. Duloxetine has provided only modest benefit and is associated with side effects and a high discontinuation rate. The 2014 American Society of Clinical Oncology CIPN guidelines provide a moderate recommendation for duloxetine treatment and recommend further research in this area.⁴New safe and effective treatments are needed.

Increased interest in CIPN has included investigation of several nonpharmaceutical interventions. This study evaluates the dietary supplement OPERA® for the treatment of CIPN. While the authors have established the effectiveness and safety of OPERA® for CIPN, there are several limiting variables. There is limited and conflicting evidence regarding the components of OPERA®. Alpha lipoic acid has been shown to increase glutathione levels and support healthy nerve tissue and blood sugar levels.⁵A powerful anti-inflammatory herb, Boswellia serrata helps balance 5-lipoxygenase (LOX) activity and support a healthy inflammatory response.⁶Methylsulfonylmethane has been shown to reduce C-fiber nerve conduction,⁷which is essential for effective pain control. It also has chemopreventive properties and anti-inflammatory activities.^8.9

No reliably effective treatment to prevent or treat CIPN symptoms has been established.

The components of OPERA® may work synergistically to improve symptoms of CIPN as they share anti-inflammatory effects, potent antioxidant properties, and potential benefits for diabetic neuropathy (nerve health and blood sugar control); however, evidence regarding the effectiveness of these components individually for CIPN use is lacking. A clear limitation of this study is its small sample size and inhomogeneous patient population. Despite these limitations, the authors claim that OPERA® reduced patients' pain perception, improved motor and sensory impairments, and was well tolerated, with no treatment-related toxicities. Unfortunately, the authors failed to statistically evaluate their results. The lack of statistical significance makes these seemingly positive results impossible to interpret.

Although the authors of this study report that OPERA® was safe and effective, these results are not significant given the lack of statistical analysis. The activity of this dietary supplement may benefit patients with CIPN, but future well-designed, prospective, randomized, controlled trials are warranted to support its use in these patients.