Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study
Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study
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DOI：
10.1093/annonc/mdp549
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发表时间：
2010-07-01
影响因子：
50.5
通讯作者：
Cervantes, A.
中科院分区：
文献类型：
--
作者：
Tabernero, J.;Ciardiello, F.;Cervantes, A.
患者和方法：该研究包括两部分：为期 6 周的西妥昔单抗单药治疗剂量递增阶段和随后的联合治疗阶段，在此期间，患者以与单药治疗阶段相同的剂量/时间表接受西妥昔单抗治疗，然后接受伊立替康加输注 5-氟尿嘧啶/亚叶酸 (FOLFIRI)。对照组患者接受西妥昔单抗初始剂量 400 mg/m(2)，然后每周 250 mg/m(2)，剂量递增组患者每两周接受 400-700 mg/m(2) 剂量的西妥昔单抗。 结果：本研究纳入了 62 名患者。未达到每两周给药一次的西妥昔单抗的 MTD。所有组的安全性均相似。西妥昔单抗单药治疗和联合治疗阶段的缓解率分别为 15% 和 42%。 500、600 mg/m(2) 和标准每周治疗方案的谷值水平相当。结论：西妥昔单抗可以安全地每两周给药一次，剂量在 400 至 700 mg/m(2) 之间，其中 500 mg/m(2) 是未来研究最方便、最可行的剂量。
Patients and methods: The study comprised two parts: a 6-week cetuximab monotherapy dose-escalation phase and a subsequent combination therapy phase, during which patients received cetuximab, at the same dose/schedule as in the monotherapy phase, followed by irinotecan plus infusional 5-fluorouracil/folinic acid (FOLFIRI). Patients in the control group received cetuximab as a 400 mg/m(2) initial dose, then 250 mg/m(2)/week and in the dose-escalation group, at 400-700 mg/m(2), every second week.Results: Sixty-two patients were included in the study. The MTD of cetuximab administered on an every-second-week schedule was not reached. The safety profiles were similar across all groups. Response rates in the cetuximab monotherapy and combination therapy phases were 15% and 42%, respectively. Trough levels for the 500, 600 mg/m(2) and standard weekly regimens were comparable.Conclusion: Cetuximab can be safely administered once every second week at doses between 400 and 700 mg/m(2), with 500 mg/m(2) being the most convenient and feasible dose for future studies.