Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial
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Chemotherapy-induced peripheral neuropathy is frequently a dose-limiting factor in cancer treatment and may cause pain and irreversible function loss in cancer survivors. We tested whether alpha-lipoic acid (ALA) could decrease the severity of peripheral neuropathy symptoms in patients undergoing platinum-based chemotherapy.
Cancer patients 18 years or older were randomly selected to receive either 600 mg ALA or a placebo three times a day orally for 24 weeks while receiving chemotherapy regimens including cisplatin or oxaliplatin. Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale and the NCI Common Toxicity Criteria for Adverse Events neurotoxicity grades. Results from timed functional tests and the Brief Pain Inventory (BPI) were secondary endpoints.
Seventy of 243 (29 %) patients completed the study (24 weeks). Both the ALA and the placebo arms had a comparable drop-out rate. No statistically significant differences were found between the ALA and the placebo groups for FACT/GOG-Ntx scores, BPI scores, and patients' functional outcomes.
This strategy of oral ALA administration was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. High attrition rates due to poor patient compliance and manner of dosage administration in this trial demonstrated a lack of feasibility for this intervention. Future studies to explore ALA as a neuroprotective agent should take heed of the barriers confronted in this study.
KeywordsChemotherapy-induced peripheral neuropathy Sensory neuropathy toxicity Alpha-lipoic acid Oxaliplatin Neuropathy
- 7.Argyriou AA, Polychronopoulos P, Koutras A, Xiros N, Petsas T, Argyriou K, Kalofonos HP, Chroni E (2007) Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy. Eur J Cancer Care (Engl) 16(3):231–237. doi:10.1111/j.1365-2354.2006.00718.x CrossRefGoogle Scholar
- 11.de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18(16):2938–2947PubMedGoogle Scholar
- 13.Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV (2013) Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population-based PROFILES registry. J Clin Oncol 31(21):2699–2707. doi:10.1200/jco.2013.49.1514 PubMedCrossRefGoogle Scholar
- 14.Land SR, Kopec JA, Cecchini RS, Ganz PA, Wieand HS, Colangelo LH, Murphy K, Kuebler JP, Seay TE, Needles BM, Bearden JD, Colman LK, Lanier KS, Pajon ER, Cella D, Smith RE, O'Connell MJ, Costantino JP, Wolmark N (2007) Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol 25(16):2205–2211. doi:10.1200/JCO.2006.08.6652 PubMedCrossRefGoogle Scholar
- 17.Kopec JA, Land SR, Cecchini R, Ganz P, Cella D, Costantino J, Wieand HS, Smith RE, Kuebler JP, Wolmark N (2006) Validation of a self-reported neurotoxicity scale in patients with operable colon cancer receiving oxaliplatin. J Support Oncol 4(8):W1–W7Google Scholar
- 25.Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D (1999) Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabetic medicine : a journal of the British Diabetic Association 16(12):1040–1043CrossRefGoogle Scholar
- 26.Ziegler D, Reljanovic M, Mehnert H, Gries FA (1999) Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association 107(7):421–430. doi:10.1055/s-0029-1212132 CrossRefGoogle Scholar
- 29.Calhoun EA, Welshman EE, Chang CH, Lurain JR, Fishman DA, Hunt TL, Cella D (2003) Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 13(6):741–748PubMedCrossRefGoogle Scholar
- 30.Cella D (1997) FACIT manual: manual of the functional assessment of chronic illness therapy (FACIT) measurement system. Center on Outcomes, Research and EducationGoogle Scholar
- 31.(CDC) CfDCaP (2011) Cancer survivors--United States, 2007. MMWR Morb Mortal Wkly Rep 60 (9):269–272Google Scholar
- 34.Atkinson TM, Mendoza TR, Sit L, Passik S, Scher HI, Cleeland C, Basch E (2010) The Brief Pain Inventory and its "pain at its worst in the last 24 hours" item: clinical trial endpoint considerations. Pain medicine (Malden, Mass) 11(3):337–346. doi:10.1111/j.1526-4637.2009.00774.x CrossRefGoogle Scholar
- 35.Program CTE (2006) Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 1 Oct 2013