Hui Y F, Reitz J
Department of Pharmacy Services, University of Michigan Medical Center, (UMMC), Ann Arbor, USA.
Am J Health Syst Pharm. 1997 Jan 15;54(2):162-70; quiz 197-8. doi: 10.1093/ajhp/54.2.162.
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m2 (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/ m2 i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer.
本文综述了吉西他滨的药理学、药代动力学、临床疗效、不良反应以及剂量与用法。吉西他滨是一种脱氧胞苷类似物抗代谢药，对某些实体瘤具有活性。吉西他滨在细胞内磷酸化为二氟脱氧胞苷三磷酸，可终止DNA链延长，并竞争性抑制DNA聚合酶和核糖核苷酸还原酶。静脉给药后，吉西他滨迅速分布至全身水分中。该药物在血浆中脱氨基成为无活性的二氟脱氧尿苷；吉西他滨和二氟脱氧尿苷主要经肾脏排泄。在临床研究中，吉西他滨可减轻晚期胰腺癌患者的疼痛并改善其功能。吉西他滨对非小细胞肺癌显示出一定活性，尤其是与顺铂或异环磷酰胺联合使用时。该药物对晚期卵巢癌和乳腺癌也显示出一定活性。不良反应包括剂量限制性骨髓抑制、流感样症状、恶心、呕吐和皮疹。吉西他滨已获得美国食品药品监督管理局（FDA）批准用于治疗局部晚期和转移性胰腺癌。该适应证的推荐剂量为1000mg/m²（以盐酸盐形式），静脉滴注30分钟，每周一次，共七周，休息一周后，每四周重复一次，剂量为1000mg/m²，静脉滴注30分钟，每周一次，共三周。吉西他滨可缓解晚期或转移性胰腺癌患者的症状。需要更多研究来确定吉西他滨在治疗非小细胞肺癌、卵巢癌和乳腺癌中的作用。
