Department of Medical Oncology, University of Manchester, Christie Hospital NHS Foundation Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Cancer Chemother Pharmacol. 2010 May;66(1):53-8. doi: 10.1007/s00280-009-1133-3. Epub 2009 Dec 3.
An intravenous (IV) erlotinib formulation has not been characterized in cancer patients but may be useful in those with gastrointestinal abnormalities that impact on the ability to take oral medication. This study sought to determine the maximum tolerated dose (MTD) of erlotinib administered as a single 30-min infusion in patients with advanced solid tumors and absolute bioavailability of erlotinib tablets at matched doses.
This was a two-center, open label, Phase I, dose-escalation and bioavailability study of single dose IV and oral erlotinib.
The highest escalated IV erlotinib dose achieved was 100 mg, with only mild adverse events reported. The MTD for IV erlotinib was not reached as a predetermined erlotinib plasma concentration cap of 4 microg/mL was exceeded in 3/6 patients. No dose-limiting toxicity was observed. Median bioavailability of erlotinib tablets was 76%.
A 100 mg single IV dose of erlotinib, given as a 30-min infusion, was well tolerated with only minor adverse events and the high level of bioavailability of oral erlotinib was confirmed.
静脉注射（IV）厄洛替尼制剂尚未在癌症患者中进行描述，但对于那些胃肠道异常影响口服药物能力的患者可能有用。本研究旨在确定在晚期实体瘤患者中单次 30 分钟输注给予厄洛替尼的最大耐受剂量（MTD），并确定匹配剂量的厄洛替尼片剂的绝对生物利用度。
这是一项两中心、开放标签、I 期、剂量递增和生物利用度研究，评估了单剂量 IV 和口服厄洛替尼。
最高递增的 IV 厄洛替尼剂量为 100mg，仅报告了轻度不良反应。由于 3/6 名患者的厄洛替尼血浆浓度达到了预设的 4μg/mL 上限，因此未达到 IV 厄洛替尼的 MTD。未观察到剂量限制毒性。厄洛替尼片剂的中位生物利用度为 76%。
单次 100mg IV 厄洛替尼，30 分钟输注，耐受性良好，仅有轻微不良反应，并且证实了口服厄洛替尼的高生物利用度。
