Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients
What this study found
Alpha-lipoic acid was associated with better neuropathy outcomes and lower cardiotoxicity and inflammation biomarkers, although left ventricular ejection fraction did not differ significantly versus placebo. Neuropathy was lower after the 9th and 12th weeks (6.3% vs 25% at both time points; p = 0.039), and Ntx-12 total scores were higher in the ALA group at week 9 (31.69 ± 2.83 vs 30.28 ± 2.29; p = 0.03) and week 12 (29.25 ± 2.44 vs 27.53 ± 1.70; p = 0.004). BNP, TNF-α, MDA, and neurotensin were all significantly better in the ALA group after intervention, while ejection fraction declined…
- Study & population
- This randomized controlled trial enrolled women with stage II-III breast cancer in Egypt receiving standard AC chemotherapy followed by weekly paclitaxel.
- Intervention
- Alpha-lipoic acid 600 mg was given orally once daily for 6 months as an adjunct to standard doxorubicin/cyclophosphamide chemotherapy followed by weekly paclitaxel, compared with placebo plus the same chemotherapy regimen.
- Key limitation
- The active-arm sample size was small, and the study was conducted in a single country and treatment setting, which limits generalizability.
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Open PDFOriginal abstract
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. 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. 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. Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. ClinicalTrials.gov: NCT03908528.