Vermorken J B, Guastalla J P, Hatty S R, Seitz D E, Tanis B, McDaniels C, Clavel M D
University Hospital Vrije Universiteit, Amsterdam, Netherlands.
Br J Cancer. 1997;76(11):1489-93. doi: 10.1038/bjc.1997.583.
Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue. As part of a series of studies to determine the maximum tolerated dose (MTD) of gemcitabine and the most appropriate schedule, a two-centre phase I study of gemcitabine was undertaken in patients with advanced refractory solid tumours using a once every 2 weeks schedule. Fifty-two patients were entered into the study at 14 different dose levels (40-5700 mg m-2). Weekly evaluations for toxicity were performed and the MTD for this once every 2 weeks schedule was 5700 mg m-2. The dose-limiting toxicity was myelosuppression, with neutropenia being most significant. Other toxicities were nausea, vomiting, fever and asthenia. One minor response was seen in a heavily pretreated breast cancer patient treated at 1200 mg m-2. Preclinical studies suggest that the efficacy of gemcitabine is more schedule than dose related, and it is concluded that this is not the most appropriate dosing schedule for gemcitabine. However, this study demonstrates the safety profile of gemcitabine, as doses over fourfold greater than that recommended for the weekly schedule of 1000 mg m-2 could be tolerated.
吉西他滨（2',2'-二氟脱氧胞苷）是一种新型核苷类似物。作为确定吉西他滨最大耐受剂量（MTD）和最合适给药方案的一系列研究的一部分，一项针对晚期难治性实体瘤患者的吉西他滨两中心I期研究采用了每2周一次的给药方案。52例患者在14个不同剂量水平（40 - 5700 mg/m²）进入研究。每周进行毒性评估，该每2周一次给药方案的MTD为5700 mg/m²。剂量限制性毒性为骨髓抑制，其中中性粒细胞减少最为显著。其他毒性包括恶心、呕吐、发热和乏力。在一名接受1200 mg/m²治疗的经过大量预处理的乳腺癌患者中观察到一个轻微缓解。临床前研究表明，吉西他滨的疗效与给药方案的关系大于与剂量的关系，得出这不是吉西他滨最合适给药方案的结论。然而，本研究证明了吉西他滨的安全性，因为其剂量超过每周1000 mg/m²推荐剂量四倍以上仍可耐受。
