A phase I study of an oral simulated FOLFOX with high dose capecitabine
A phase I study of an oral simulated FOLFOX with high dose capecitabine
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DOI：
10.1007/s10637-008-9210-8
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发表时间：
2009-10-01
影响因子：
3.4
通讯作者：
Wilding, G.
中科院分区：
文献类型：
--
作者：
Mulkerin, D.;LoConte, N. K.;Wilding, G.
背景：一项为期2天的高剂量卡培他滨联合奥沙利铂、推注5 - 氟尿嘧啶（5FU）和亚叶酸钙（LV）的I期研究旨在模拟FOLFOX6方案，且无需输注5FU。方法：方案A包括奥沙利铂100 mg/m²、5FU 400 mg/m²和LV 20 mg/m²（均在第1天和第15天静脉注射，28天为一个周期）。卡培他滨在第1天和第15天每8小时口服一次，共6次。方案B不包括5FU和LV，保留奥沙利铂和卡培他滨。对每个方案中的6名患者进行卡培他滨的药代动力学研究。结果：共治疗36名患者。观察到的剂量限制性毒性包括恶心、脱水、疲劳、低血压和意识模糊。掌跖红斑感觉异常较轻。骨髓抑制常见，但不是剂量限制性毒性。卡培他滨的药代动力学参数未改变。结论：使用卡培他滨模拟FOLFOX6是可行的，且耐受性良好，其毒性特征与标准的14天卡培他滨给药方案不同，掌跖红斑感觉异常较轻。卡培他滨联合奥沙利铂、5FU和LV的II期剂量为1500 mg/m²/次，在无推注5FU/LV时为2250 mg/m²/次。
Background: A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU. Methods: Schedule A included oxaliplatin 100 mg/m(2), 5FU 400 mg/m(2), and LV 20 mg/m(2) (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h x 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule. Results: 36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered. Conclusion: Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m(2)/dose or 2,250 mg/m(2)/dose in the absence of bolus 5FU/LV.