Bradfield Scott M, Sandler Eric, Geller Thomas, Tamura Roy N, Krischer Jeffrey P
Division of Hematology-Oncology, Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida.
Pediatr Blood Cancer. 2015 Jun;62(6):1004-10. doi: 10.1002/pbc.25384. Epub 2014 Dec 24.
Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known.
We performed a randomized, placebo-controlled, double-blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity.
Between 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity.
Vincristine-associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre-adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone.
长春新碱会引发外周感觉、运动、自主神经及颅神经病变等已知的副作用。目前尚无预防性干预措施。
我们进行了一项随机、安慰剂对照、双盲试验，研究对象为接受长春新碱治疗至少连续9周的小儿癌症患者（第1组=肾母细胞瘤和横纹肌肉瘤）或连续4周联合使用类固醇的患者（第2组=急性淋巴细胞白血病和非霍奇金淋巴瘤），口服谷氨酸作为预防剂。在指定时间点，使用改良的巴利斯小儿外周神经病变量表进行评分神经学检查，以记录神经毒性。
2007年至2012年期间，共纳入250例患者（第1组=50例，第2组=200例）。总体而言，以及在各层或年龄亚组中，谷氨酸治疗组的神经毒性百分比与安慰剂治疗组相比均无显著降低。唯一提示有治疗效果的亚组是年龄。13岁及以上的患者与年龄小于13岁的患者相比（P = 1.00），谷氨酸治疗显示出更大的益处（P = 0.055）。便秘是最常报告的（14%）II级或更高等级的神经毒性。
小儿肿瘤学中长春新碱相关的神经毒性仍然是多种诊断化疗的常见并发症，约30%的患者受影响。谷氨酸对青春期前儿童预防无效。13岁及以上患者有获益的迹象，但该研究并非专门设计用于单独检验该年龄组内的治疗效果。
