Sartori S, Trevisani L, Nielsen I, Tassinari D, Abbasciano V
Dipartimento di Medicina e Oncologia Medica, Osp. S. Anna, Ferrara, Italy.
Cancer. 1996 Oct 1;78(7):1477-82. doi: 10.1002/(sici)1097-0142(19961001)78:7<1477::aid-cncr15>3.0.co;2-x.
Chemotherapy (CT) may induce acute mucosal injury to the stomach and duodenum, but its prevention has been scarcely investigated.
One hundred and eighty-two cancer patients with normal stomach and duodenum or having fewer than 3 erosions, selected to be treated with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (77 breast carcinoma patients) or 5-fluorouracil (5-FU) (105 colon carcinoma patients), were randomly assigned to prophylactic treatment with misoprostol, 400 micrograms twice a day; omeprazole, 20 mg once a day; or placebo, 1 tablet twice a day. Seven days after the end of the second source of CT, all patients underwent control esophagogastroduodenoscopy. Endoscopic findings were quantified on the basis of an arbitrary score: 0 = normal; 1 = less than 3 erosions; 2 = 3-15 erosions; 3 = more than 15 erosions or ulcer; 4 = giant ulcer (greatest dimension of more than 2 cm) or multiple ulcers with cumulative greatest dimension exceeding 2 cm.
Mean score increased significantly in the placebo and misoprostol groups, either after CMF (P < 0.001 and P < 0.05, respectively) or after 5-FU (P < 0.001 for both), whereas it did not in the omeprazole group. Gastric and duodenal ulcers were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.05 after both CMF and 5-FU). No significant difference was observed between placebo and misoprostol. Omeprazole was significantly more effective than placebo and misoprostol in reducing the frequency and degree of the endoscopic worsening, either after CMF or after 5-FU (P < 0.05 for both CT regimens). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.01) or misoprostol (P < 0.001).
The strong and prolonged inhibition of gastric acid production induced by omeprazole seems to be effective in preventing chemotherapy-induced gastroduodenal mucosal injury. Further trials are necessary to verify whether such a prevention of endoscopically observed injury can translate into prevention of clinically significant injury.
化疗（CT）可能会导致胃和十二指肠急性黏膜损伤，但其预防措施鲜有研究。
182例胃和十二指肠正常或糜烂少于3处的癌症患者，入选接受环磷酰胺、甲氨蝶呤和5-氟尿嘧啶（CMF）治疗（77例乳腺癌患者）或5-氟尿嘧啶（5-FU）治疗（105例结肠癌患者），被随机分配接受米索前列醇预防性治疗，每日2次，每次400微克；奥美拉唑，每日1次，每次20毫克；或安慰剂，每日2次，每次1片。在第二个化疗疗程结束7天后，所有患者接受食管胃十二指肠镜检查。内镜检查结果根据任意评分进行量化：0 = 正常；1 = 少于3处糜烂；2 = 3 - 15处糜烂；3 = 超过15处糜烂或溃疡；4 = 巨大溃疡（最大直径超过2厘米）或多个溃疡，累积最大直径超过2厘米。
安慰剂组和米索前列醇组的平均评分在接受CMF或5-FU治疗后均显著升高（分别为P < 0.001和P < 0.05以及两者P < 0.001），而奥美拉唑组未升高。接受奥美拉唑治疗的患者发生胃和十二指肠溃疡的频率显著低于接受安慰剂治疗的患者（CMF和5-FU治疗后均为P < 0.05）。安慰剂组和米索前列醇组之间未观察到显著差异。在减少内镜下病情恶化的频率和程度方面，无论是在接受CMF还是5-FU治疗后，奥美拉唑均显著优于安慰剂和米索前列醇（两种化疗方案均为P < 0.05）。接受奥美拉唑治疗的患者出现上腹部疼痛和/或烧心的频率显著低于接受安慰剂治疗的患者（P < 0.01）或米索前列醇治疗的患者（P < 0.001）。
奥美拉唑对胃酸分泌的强效和持久抑制似乎对预防化疗引起的胃十二指肠黏膜损伤有效。需要进一步试验来验证这种对内镜观察到的损伤的预防是否能转化为对具有临床意义的损伤的预防。
