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 9th and 12th 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.

Effect of cilostazol on preventing paclitaxel‐induced neuropathy in patients with breast cancer: A randomized controlled trial

“…This is conceivably linked to chemotherapy side effects and development of neuropathy. Worsening in patients' QoL with chemotherapy, comparable to that reported in the present study, was previously reported when breast cancer patients administered taxanes 37,38 . Cilostazol administration was linked to less worsening effects in patients' QoL.…”

“…TA B L E 1 (Continued) NCI-CTCAE neuropathy grading, a valid patient reported outcome measure, 36 this approach was widely used in similar clinical trials assessing other different pharmacological interventions. 37,38 Our results were in favor of the preventive role of cilostazol at which the incidence of grade 2 or 3 neuropathy reported by our patients was 40% in the cilostazol arm compared to 86.7% in the placebo arm (p < 0.001). There was also longer time to develop symptoms of neuropathy in the cilostazol arm over the control arm.…”

“…The difference in the incidence of grade two or three PN was taken as a primary endpoint. The grading were done according to NCI‐CTCAE neuropathy grading, a valid patient reported outcome measure, 36 this approach was widely used in similar clinical trials assessing other different pharmacological interventions 37,38 …”

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

“…Dietary changes do not alter nutrient levels in tumors and healthy tissues in a balanced manner. Further, similar to new drug combinations, the combination of dietary nutrients and DOX must be adapted based on the specific tumor and its metabolic activity, and clinical trials are required before an optimal anticancer regimen may be identified [ 111 ]. Here, we summarize the specific mechanisms by which vitamins, fatty acids, glucose analogs, and the micronutrient selenium regulate DIC and DOX resistance via p53.…”

Vitamins in neuropathy: pathophysiological and therapeutic roles

“…In addition, a-lipoic acid (a-LA), considered as a B vitamin because of the similarity in structure and function, was reported to play important roles in peripheral neuropathy because of nerve injury [27], T2DM [28,29], CIPN by various drugs [30][31][32]. a-LA may exert its neuroprotection through reducing oxidative stress, neuronal apoptosis [29], and the axon demyelination, protecting axons from demyelination [33 & ], and accelerating the process of nerve healing [27].…”