Bourhis Jean, Rivera Fernando, Mesia Ricard, Awada Ahmad, Geoffrois Lionel, Borel Christian, Humblet Yves, Lopez-Pousa Antonio, Hitt Ricardo, Vega Villegas M Eugenia, Duck Lionel, Rosine Dominique, Amellal Nadia, Schueler Armin, Harstrick Andreas
Institut Gustave Roussy, Radiothérapie, Villejuif, France.
J Clin Oncol. 2006 Jun 20;24(18):2866-72. doi: 10.1200/JCO.2005.04.3547. Epub 2006 May 22.
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).
Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) 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/m2/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.
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.
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/m2/d in combination with cisplatin or carboplatin can be recommended for additional studies.
这是一项开放、随机、多中心的I/II期研究，旨在调查西妥昔单抗用于一线治疗复发/转移性头颈部鳞状细胞癌（SCCHN）的安全性和耐受性。
治疗方案为西妥昔单抗（初始剂量400mg/m²，随后每周剂量250mg/m²）联合每3周一个周期的顺铂（100mg/m²）或卡铂（曲线下面积为5），每种方案均联合5天输注氟尿嘧啶（FU），剂量递增，分别为600、800和1000mg/m²/天。该研究分为两个阶段：A阶段，前两个周期（6周）重点关注联合治疗的安全性和耐受性；B阶段，其余时间用于那些从治疗中获益的患者，直至疾病进展或出现无法耐受的毒性。
53例患者入组本研究。A阶段剂量限制性毒性的发生率可以接受。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已知的安全性特征相符。患者的总体缓解率为百分之三十六，在最高剂量的FU下未观察到疗效增加的明显趋势，同时化疗方案对西妥昔单抗的药代动力学也没有影响。
西妥昔单抗、顺铂/卡铂和FU的联合方案耐受性良好，对复发/转移性SCCHN有活性，值得进一步研究。可推荐将1000mg/m²/天的FU剂量与顺铂或卡铂联合用于进一步研究。
