May 21, 2022Open Access

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

RWRehab H. WeridaDamanhour University REReham A. ElshafieyDamanhour University AGAsser I. GhoneimPharos University in Alexandria

Structured PICO

Does alpha-lipoic acid reduce paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer?

Population

64 women with stage II and stage III breast cancer, mean age ~49, ECOG performance status <2, adequate hematologic, liver, and renal function, without prior exposure to anthracyclines or neurotoxic agents.

Intervention

Alpha-lipoic acid (ALA) 600 mg oral once daily for 6 months added to chemotherapy (4 cycles of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days, followed by weekly paclitaxel 80 mg/m2 for 12 weeks).

Comparator

Matching placebo tablets once daily for 6 months added to the same chemotherapy regimen.

Outcome

Percentage of patients with peripheral sensory neuropathy grade > 2 (assessed by NCI-CTCAE v4.0) and variation of 12-item neurotoxicity questionnaire (Ntx-12) total score.patient reported

Alpha-lipoic acid supplementation during chemotherapy in breast cancer patients significantly attenuated paclitaxel-induced peripheral neuropathy and reduced biomarkers of doxorubicin-induced cardiotoxicity, though it did not prevent the decline in ejection fraction.

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: 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.

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