Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients

Abstract Background and objective Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer. Patients and methods This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group ( n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group ( n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t- test, Mann–Whitney U test, and chi-square test. Results As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9 th and 12 th weeks of paclitaxel intake ( p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin ( p < 0.05) as compared to baseline data and placebo. Conclusion Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. Trial registration ClinicalTrials.gov: NCT03908528.