Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1200/jco.2005.04.3547
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发表时间：
2006-06-20
影响因子：
45.3
通讯作者：
Harstrick, Andreas
中科院分区：
文献类型：
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作者：
Bourhis, Jean;Rivera, Fernando;Harstrick, Andreas
目的 这是一项开放、随机、多中心 I/II 期研究，旨在调查西妥昔单抗一线治疗复发性/转移性头颈鳞状细胞癌 (SCCHN) 的安全性和耐受性。 患者和方法 治疗包括西妥昔单抗（初始剂量 400 mg/m(2)，随后每周剂量 250 mg/m2）联合 3 周周期的顺铂(100 mg/m(2)) 或卡铂（曲线下面积，5），分别与 5 天的氟尿嘧啶 (FU) 输注组合，剂量递增为 600、800 和 1,000 mg/m(2)/天。该研究分为两个阶段：A、前两个周期（6周）重点关注联合治疗的安全性和耐受性； B，从治疗中受益的患者直到疾病进展或无法耐受的毒性的剩余时间。 结果 53 名患者参加了该研究。 A 期剂量限制性毒性的发生率是可以接受的。两组中最常见的 3/4 级不良事件为白细胞减少 (38%)、乏力 (25%)、呕吐 (14%) 和血小板减少 (15%)，这与西妥昔单抗、顺铂/卡铂和 FU 的已知安全性一致。患者的总体缓解率为 36%，最高剂量 FU 的疗效没有明显增加的趋势，并且联合化疗方案对西妥昔单抗药代动力学没有影响。 结论 西妥昔单抗、顺铂/卡铂和 FU 联合治疗复发/转移性 SCCHN 具有良好的耐受性和活性，值得进一步研究。可以推荐 1,000 mg/m(2)/d 的 FU 剂量与顺铂或卡铂联合用于其他研究。
Purpose This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).Patients and Methods Treatment comprised cetuximab (initial dose 400 mg/m(2) with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m(2)) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m(2)/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.Results Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics.Conclusion The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m(2)/d in combination with cisplatin or carboplatin can be recommended for additional studies.