Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Med Oncol. 2011 Dec;28(4):1136-9. doi: 10.1007/s12032-010-9598-9. Epub 2010 Jun 22.
Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 58 year old woman with metastatic rectal carcinoma who developed severe gastrointestinal toxicity when the thus far well-tolerated intravenous 5-fluorouracil (5-FU)/leucovorin containing chemotherapeutic regimen was replaced by the same chemotherapeutic regimen in combination with the oral 5-FU prodrug capecitabine. This increased toxicity is probably due to the intracellular retention of polyglutamated folates induced by prior leucovorin therapy which, upon subsequent administration of capecitabine, will result in an enhanced and prolonged inhibition of the, for DNA synthesis important, enzyme thymidylate synthase, essentially creating a situation equivalent to overdosing.
结直肠癌是最常见的肿瘤类型之一，一般在转移性疾病的情况下采用姑息化疗进行治疗。在这里，我们描述了一位 58 岁女性转移性直肠癌的病例，当她原本耐受良好的静脉注射氟尿嘧啶（5-FU）/亚叶酸方案更换为相同的化疗方案，同时联合应用氟尿嘧啶前体药物卡培他滨时，出现了严重的胃肠道毒性。这种毒性增加可能是由于先前亚叶酸治疗诱导的多谷氨酸化叶酸在细胞内的蓄积，随后给予卡培他滨会导致对 DNA 合成重要的酶胸苷酸合成酶的增强和延长抑制，实质上造成了相当于药物过量的情况。
