WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment
WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment
复制标题
DOI：
10.1385/ijgc:29:1:19
复制
发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Mason, KA
中科院分区：
文献类型：
--
作者：
Phan, TP;Crane, CH;Mason, KA
背景核苷类似物吉西他滨是一种有效的肿瘤和正常粘膜的放射增敏剂，因此在胰腺癌的一些临床治疗方案中，其与放射的组合导致了严重的毒性反应。WR-2721（氨磷汀）已被证明可以减少放射治疗和某些化疗药物产生的正常组织毒性。本研究的目的是确定WR-2721是否可以保护胃肠道粘膜免受吉西他滨和放射治疗的损伤。在全身照射前24 h，将吉西他滨以33 mg/kg的浓度ip注射到C3 Hf/Karn小鼠中。在放射治疗前30分钟或吉西他滨前30分钟或在这两个时间给予WR-2721的单剂量（200 mg/kg）。使用小鼠微集落测定法对肠隐窝中的干细胞存活进行了化疗/放射诱导的损伤的定量评估。结果在吉西他滨前30分钟给予WR-2721，24小时后给予辐射，对空肠没有任何保护作用（DMF 0.95）。然而，WR-2721在放射前30分钟给药，无或与先前的吉西他滨产生的保护因子（PF）为1.35和1.42。WR-2721不能直接保护胃肠道粘膜免受吉西他滨毒性的影响，但它确实保护吉西他滨放射致敏粘膜免受急性放射损伤，保护系数为1.42。因此，在使用吉西他滨同时放化疗的临床治疗方案中，WR-2721可能具有预防辐射诱导的粘膜毒性的临床效用。
Background. The nucleoside analog gemcitabine is a potent radiosensitizer of both tumor and normal mucosa, so severe toxic reactions have resulted from its combination with radiation in some clinical treatment schedules for pancreatic cancer. WR-2721 (amifostine) has been shown to reduce normal tissue toxicity produced from both radiation treatment and some chemotherapeutics. The aim of this study was to determine if WR-2721 can protect the gastrointestinal mucosa from injury by concurrent gemcitabine and radiation treatment.Methods and Materials. Gemcitabine was injected ip into C3Hf/Karn mice at a concentration of 33 mg/kg 24 h before whole-body irradiation. A single dose (200 mg/kg) of WR-2721 was given 30 min before the radiation treatment or 30 min before gemcitabine or at both times. A quantitative assessment of the chemotherapy/radiation-induced damage was carried out using the mouse microcolony assay for stem cell survival in the intestinal crypts. Results. WR-2721 given 30 min before gemcitabine followed 24 h later by radiation did not confer any protection to the jejunum (DMF 0.95). However, WR-2721 administered 30 min before radiation without or with prior gemcitabine produced protection factors (PF) of 1.35 and 1.42Conclusions. WR-2721 did not directly protect the gastrointestinal mucosa from gemcitabine toxicity, but it did protect the gemeitabine-radiosensitized mucosa from acute radiation damage by a factor of 1.42. Therefore, in clinical treatment protocols using concurrent chemoradiation with gemcitabine, WR-2721 may have clinical utility in protecting against radiation-induced mucosal toxicity.