N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data

Abstract

Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Oxaliplatin-Induced Neuropathy: Oxidative Stress as Pathological Mechanism. Protective Effect of Silibinin

“…7,29,38 It remains to be seen if their therapeutic limited effectiveness is due to the scarce activity of the presently available substances or to the complexity of oxaliplatin neurotoxicity where oxidative stress could be only an epiphenomenon.…”

“…In particular, glutathione, N-acetylcysteine, and vitamin E (a-tocopherol) may have a clinical role in patient neuroprotection. 4,6,7,25,29,35 However, the major bias of these clinical trials resides in their small size and/ or in their short term follow-up. 2 An important limit in this field is the insufficient information on the molecular basis of the neuropathy.…”

Obwodowa neuropatia wywołana chemioterapią. Część II. Zapobieganie

“…Znaleziono tylko jedno badanie oceniające pozytywny wpływ tego typu profilaktyki u pacjentów podczas terapii oksaliplatyną [27], lecz mała liczba pacjentów nie pozwala realnie ocenić bezpieczeństwa tego leku.…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…In a further study conducted with NAC no significant changes on electrophysiological testing on both sensory and motor nerves were found between the two groups [259].…”

“…N-acetyl cysteine (NAC) administration to cancer patients has been based on the assumption that NAC can increase glutathione production, an effect that may decrease cyto-toxicity [259].…”