ASSESSMENT OF THE ROLE OF ALPHALIPOIC ACID IN PREVENTION OF CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY

Marwa A. Suliman, Aml M. EL-Sharkasy, Ehab M. Hassanin and Maha L. Zamzam. Clinical Oncology & Nuclear Medicine Department, Faculty of Medicine, Suez Canal University, Egypt. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 05 January 2018 Final Accepted: 07 February 2019 Published: March 2019


Int. J. Adv. Res. 7(3), 179-184
180 Introduction:-Chemotherapy induced peripheral neuropathy is considered a common dose limiting side effect of many chemotherapeutic agents. It is considered the second most common acute toxicity after hematologic toxicity (Windebank &Grisold, 2008).It affects about 30 % of patients treated by chemotherapy. Although it is not a life threatening complication but it affects the quality of life and daily activities e.g. buttoning a shirt (Seretny et al., 2014).CIPN manifests clinically as deficits in motor, autonomic, sensory or less likely, functions. The incidence mainly related to the dose and the used chemotherapeutic agent and it also affected if there is preexisting nerve damage from other causes (such as diabetes mellitus, previous exposure to neurotoxic drugs).Also motor manifestations may occur in the form of weakness of the extremities (such as foot drop), and autonomic manifestations may occur in the form of orthostatic hypotension (Kaley & DeAngelis, 2009).
Dose reduction or alteration of a potentially curative chemotherapeutic agent usually occurs due to this side effect. However treatments to this condition (such as amfostine, anti-depressant drugs…) have been found to be ineffective and have many side effects. The most common used CIPN agents include (platinum drugs, taxanes, vincaalkaloids, thalidomide, bortezomib, interferon, methotrexate, fluorouracil, cytarbine) ( Simão DAdS et al.,2015).
Alpha Lipoic acid is a physiological anti-oxidant that has been found effective in diabetic neuropathy, but isn't investigated thoroughly for the use in CIPN. ALA is easy to be transported across all membranes as it is a fat-and water soluble, and exerts its antioxidant activity inside and outside of cells (Guo et al., 2014).

Materials and Methods:-
It was a prospective clinical trial conducted at Clinical Oncology Department in Suez Canal University Hospital, done to assess role of alpha lipoic acid in prevention of CIPN where one hundred patients received chemotherapy causing peripheral neuropathy were included in our study. The target population included adult patients who attended clinical oncology department in Suez Canal university hospital, they were divided into two equal groups, study and control group where 50 of eligible patients were assigned to each of the 2 groups.
Group (A): The Study group: Patients who received chemotherapeutic drugs causing peripheral neuropathy received alpha lipoic acid 6oo mg three times daily for 12 weeks from the start of chemotherapy.
Group (B): control group, Patients who received chemotherapeutic drugs causing peripheral neuropathy but didn't take alpha lipoic acid.

Inclusion criteria:
Patients planned to receive chemotherapy known to cause peripheral neuropathy (vincristine, taxanes and platinum derivatives), any stage of the disease, adult patients (aged between 18 and 65 years old), expected survival of the patients more than one year and patients have normal liver and renal function.

Exclusion criteria:
Patients known to have diabetes, preexisting neurologic condition that would complicate interpretation, presence of peripheral nerve damage due to other disease or treatment, patients received previously neurotoxic chemotherapeutic drugs, patients already on treatment for neuropathy, patients known to have spinal cord compression or brain lesion,and patients known to be allergic, patients refused to be included the study.
Assessment was done before starting treatment and after each cycle.Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale (Wampler, 2016).

Summary
Functional Assessment of Cancer Therapy/ Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx) (v4) • An 11-item patient self-report tool that describes CIPN symptom severity and functional consequences. • 0-44 points, a lower score indicates better quality of life 181 Demographic data: Age, sex, residence, performance using ECOG-PS score, educational level of the patient.

Data related to disease:
Pathology of primary disease, presence of bone metastasis that would cause numbness, presence of pre-existing neurologic disease, presence of any other metastasis.

Data related to Management:
Onset, severity of neuropathy and efficacy of treatment in CIPN.
Post management: Outcome was rated using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale.    Table 3 shows the types of chemotherapy that was used in the enrolled patients, in the control group single agent causing CIPN was used in 64% of patients while 36% of them had combined therapy causing CIPN, the most commonly used were Taxanes. In the study group single therapy was used in 66% of patients, the most common 182 used medications were Taxanes which was used in 42% of patients and Platinum compounds which was used in 18% of patients.   Table 4&Figure 1. shows statistical significance difference in mean FACT/GOG-Ntx score of neuropathies in 2 nd and 3 rd follow up between both control and study groups, (p-value<0.001) where study group had a lower mean score than control group.

Discussion:-
CIPN is considered one of the most debilitating side-effect of chemotherapy and mostly worsening the patients' quality of life and if severe enough leads to decrease dose or change the type of the used curative chemotherapy (Hausheer et al., 2006).
Alpha lipoic acid has strong chelating, antioxidant activity, and neuroprotective and neurotrophic properties; therefore, it can eliminate the free radicals produced by chemotherapy, re-activate the normal axonal flow and reduce the neuropathic anticancer therapies effects (Bilska, A. et al., 2005).
In this trial, we investigated ALA to determine if its use decreases the severity of peripheral neuropathy and if it improves the quality of life after patients' exposure to twelve weeks of chemotherapy.
The study was conducted at clinical Oncology department in Suez Canal university hospital over a period of one year. Our study included 100 eligible patients which was more than the number of patients found in a study done in Italy where the number of patients were 25 adult treated at the Radiation Oncology Unit of the Careggi University P-value<0.001 P-value<0.001 P-value=0.11 P-value=0.53