Dagdemir Ayhan, Yildirim Hasan, Aliyazicioglu Yuksel, Kanber Yilmaz, Albayrak Davut, Acar Sabri
Medical Faculty, Department of Pediatric Oncology, Ondokuz Mayis University, 55139 Kurupelit-Samsun, Turkey.
Support Care Cancer. 2004 Apr;12(4):263-7. doi: 10.1007/s00520-004-0591-8. Epub 2004 Feb 6.
Our aim was to explore whether vitamin A has protective effect on high-dose-methotrexate (HDMTX)-induced intestinal D-xylose malabsorption in children with leukemia and lymphoma.
We performed a prospective randomized un-blinded study of vitamin A in 35 children with leukemia and lymphoma who were planned to receive HDMTX 3 g/m(2) and 5 g/m(2), respectively. Twenty-two patients (group 1) received a single dose of 180,000 IU a day before HDMTX was given, and 13 (group 2) received only HDMTX. The vitamin A group received the vitamin only once. Oral D-xylose absorption tests before and 7 days after HDMTX were carried out to evaluate intestinal absorption. Retinol-binding protein (RBP) levels prior to therapy were also measured for vitamin A status.
Although we observed no difference of HDMTX-induced toxicity, including hematological, dermatological, systemic, and other toxicities, between groups, the D-xylose absorption test was significantly better in-group 1 ( p=0.030). Absorption was decreased in five of 22 patients (23%) who received vitamin A comparing to eight of 13 (62%) who received only HDMTX ( p=0.033). RBP levels were lower than normal in 13 of 22 patients in-group 1 and nine of 13 in group 2. In patients whose RBP levels were lower than normal, HDMTX-induced toxicity was lower in the group 1 than group 2 but not statistically significant. No sign of vitamin A toxicity was observed throughout the study.
The administration of vitamin A before HDMTX may protect against drug-induced D-xylose malabsorption in children with cancer. Further studies are apparently needed to clarify the full benefits of vitamin A in preventing HDMTX-induced mucosal damage.
我们的目的是探讨维生素A对白血病和淋巴瘤患儿高剂量甲氨蝶呤(HDMTX)诱导的肠道D-木糖吸收不良是否具有保护作用。
我们对35例计划分别接受3 g/m²和5 g/m² HDMTX治疗的白血病和淋巴瘤患儿进行了一项关于维生素A的前瞻性随机非盲研究。22例患者(第1组)在给予HDMTX前一天接受单剂量180,000 IU维生素A,13例(第2组)仅接受HDMTX。维生素A组仅接受一次维生素。在HDMTX治疗前及治疗后7天进行口服D-木糖吸收试验以评估肠道吸收情况。还测量了治疗前的视黄醇结合蛋白(RBP)水平以评估维生素A状态。
尽管我们观察到两组之间在HDMTX诱导的毒性方面无差异,包括血液学、皮肤学、全身性及其他毒性,但第1组的D-木糖吸收试验结果明显更好(p = 0.030)。接受维生素A的22例患者中有5例(23%)吸收下降,而仅接受HDMTX的13例患者中有8例(62%)吸收下降(p = 0.033)。第1组22例患者中有13例RBP水平低于正常,第2组13例中有9例。在RBP水平低于正常的患者中,第1组HDMTX诱导的毒性低于第2组,但无统计学意义。在整个研究过程中未观察到维生素A毒性迹象。
在HDMTX治疗前给予维生素A可能预防癌症患儿药物诱导的D-木糖吸收不良。显然需要进一步研究以阐明维生素A在预防HDMTX诱导的黏膜损伤方面的全部益处。