Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients

被引:143
作者
Wang, Wei-Shu
Lin, Jen-Kou
Lin, Tzu-Chen
Chen, Wei-Shone
Jiang, Jeng-Kae
Wang, Huann-Sheng
Chiou, Tzeon-Jye
Liu, Jin-Hwang
Yen, Chueh-Chuan
Chen, Po-Min [1 ]
机构
[1] Taipei Vet Gen Hosp, Dept Med, Div Hematol & Oncol, Taipei, Taiwan
[2] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan
[3] Taipei Vet Gen Hosp, Dept Surg, Div Colorectal Surg, Taipei, Taiwan
关键词
colorectal carcinoma; glutamine; neuropathy; oxaliplatin;
D O I
10.1634/theoncologist.12-3-312
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oxaliplatin is effective in the treatment of metastatic colorectal cancer (MCRC) patients; however, severe neurotoxicity develops frequently. To assess the efficacy of oral glutamine for preventing neuropathy induced by oxaliplatin, a pilot study was performed. A total of 86 patients with MCRC treated at Taipei Veterans General Hospital were enrolled. Oxaliplatin (85 mg/m(2), days 1 and 15) plus weekly bolus 5-fluorouracil (5-FU; 500 mg/m(2)) and folinic acid (FA; 20 mg/m(2)) on days 1, 8, and 15 were given every 28 days as first-line treatment. Patients were randomized to receive (glutamine group; n = 42) or not receive (control group; n = 44) glutamine (15 g twice a day for seven consecutive days every 2 weeks starting on the day of oxaliplatin infusion). Efficacy of chemotherapy, neurological toxicity, and electrophysiological alterations were assessed. A lower percentage of grade 1-2 peripheral neuropathy was observed in the glutamine group (16.7% versus 38.6%) after two cycles of treatment, and a significantly lower incidence of grade 3-4 neuropathy was noted in the glutamine group after four cycles (4.8% versus 18.2%) and six cycles (11.9% versus 31.8%). By adding glutamine, interference with activities of daily living was lower (16.7% versus 40.9%), and need for oxaliplatin dose reduction was lower (7.1% versus 27.3%). There were no significant between-group differences in response to chemotherapy (52.4% versus 47.8%), electrophysiological abnormalities, grade 3-4 non-neurological toxicities (26.2% versus 22.8%), or survival. These data indicate that oral glutamine significantly reduces the incidence and severity of peripheral neuropathy of MCRC patients receiving oxaliplatin without affecting response to chemotherapy and survival.
引用
收藏
页码:312 / 319
页数:8
相关论文
共 41 条
[1]   Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: A North Central Cancer Treatment Group Phase II study [J].
Alberts, SR ;
Horvath, WL ;
Stcrnfeld, WC ;
Goldberg, RM ;
Mahoney, MR ;
Dakhil, SR ;
Levitt, R ;
Rowland, K ;
Nair, S ;
Sargent, DJ ;
Donohue, JH .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (36) :9243-9249
[2]   Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer [J].
Andre, T ;
Boni, C ;
Mounedji-Boudiaf, L ;
Navarro, M ;
Tabernero, J ;
Hickish, T ;
Topham, C ;
Zaninelli, M ;
Clingan, P ;
Bridgewater, J ;
Tabah-Fisch, I ;
de Gramont, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2343-2351
[3]   NERVE GROWTH-FACTOR PREVENTS TOXIC NEUROPATHY IN MICE [J].
APFEL, SC ;
LIPTON, RB ;
AREZZO, JC ;
KESSLER, JA .
ANNALS OF NEUROLOGY, 1991, 29 (01) :87-90
[4]   EFFECT OF GLUTAMINE ON TUMOR AND HOST GROWTH [J].
BARTLETT, DL ;
CHARLAND, S ;
TOROSIAN, MH .
ANNALS OF SURGICAL ONCOLOGY, 1995, 2 (01) :71-76
[5]   INTRACELLULAR FREE AMINO-ACID CONCENTRATION IN HUMAN MUSCLE-TISSUE [J].
BERGSTROM, J ;
FURST, P ;
NOREE, LO ;
VINNARS, E .
JOURNAL OF APPLIED PHYSIOLOGY, 1974, 36 (06) :693-697
[6]  
Boyle FM, 1996, J PHARMACOL EXP THER, V279, P410
[7]   Amelioration of experimental cisplatin and paclitaxel neuropathy with glutamate [J].
Boyle, FM ;
Wheeler, HR ;
Shenfield, GM .
JOURNAL OF NEURO-ONCOLOGY, 1999, 41 (02) :107-116
[8]   Glutamine protects against doxorubicin-induced cardiotoxicity [J].
Cao, YH ;
Kennedy, R ;
Klimberg, S .
JOURNAL OF SURGICAL RESEARCH, 1999, 85 (01) :178-182
[9]   Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo-controlled trial [J].
Cascinu, S ;
Catalano, V ;
Cordella, L ;
Labianca, R ;
Giordani, P ;
Baldelli, AM ;
Beretta, GD ;
Ubiali, E ;
Catalano, G .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (16) :3478-3483
[10]   XELOX (capecitabine plus oxaliplatin):: Active first-line therapy for patients with metastatic colorectal cancer [J].
Cassidy, J ;
Tabernero, J ;
Twelves, C ;
Brunet, R ;
Butts, C ;
Conroy, T ;
Debraud, F ;
Figer, A ;
Grossmann, J ;
Sawada, N ;
Schöffski, P ;
Sobrero, A ;
Van Cutsem, E ;
Diaz-Rubio, E .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (11) :2084-2091