title: 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.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taiwan, Republic of China.
authors.forename: Peng-Chan
authors.initials: PC
authors.lastname: Lin
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lee
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Wang
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Chao
authors.forename: Liang-Tsai
authors.initials: LT
authors.lastname: Hsiao
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
authors.forename: Kon-Ping
authors.initials: KP
authors.lastname: Lin
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010865:Pilot Projects; D011182:Postoperative Care
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000111:Acetylcysteine