Vermorken Jan B, Mesia Ricard, Rivera Fernando, Remenar Eva, Kawecki Andrzej, Rottey Sylvie, Erfan Jozsef, Zabolotnyy Dmytro, Kienzer Heinz-Roland, Cupissol Didier, Peyrade Frederic, Benasso Marco, Vynnychenko Ihor, De Raucourt Dominique, Bokemeyer Carsten, Schueler Armin, Amellal Nadia, Hitt Ricardo
Antwerp University Hospital, Department of Medical Oncology, Edegem, Belgium.
N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first.
Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths.
As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)
西妥昔单抗对铂类耐药的复发性或转移性头颈部鳞状细胞癌有效。我们研究了西妥昔单抗联合铂类化疗作为复发性或转移性头颈部鳞状细胞癌患者一线治疗的疗效。
在442例符合条件的未经治疗的复发性或转移性头颈部鳞状细胞癌患者中，我们随机分配220例患者接受顺铂（第1天剂量为每平方米体表面积100 mg）或卡铂（曲线下面积为每毫升每分钟5 mg，第1天静脉输注1小时）加氟尿嘧啶（剂量为每天每平方米1000 mg，共4天），每3周一次，最多6个周期；222例患者接受相同化疗加西妥昔单抗（初始剂量为每平方米400 mg，静脉输注2小时，然后每周静脉输注1小时，剂量为每平方米250 mg），最多6个周期。接受化疗加西妥昔单抗且病情稳定的患者继续接受西妥昔单抗治疗，直至疾病进展或出现不可接受的毒性作用，以先发生者为准。
在铂类化疗加氟尿嘧啶（铂-氟尿嘧啶）基础上加用西妥昔单抗显著延长了中位总生存期，从单纯化疗组的7.4个月延长至接受化疗加西妥昔单抗组的10.1个月（死亡风险比为0.80；95%置信区间为0.64至0.99；P=0.04）。加用西妥昔单抗使中位无进展生存期从3.3个月延长至5.6个月（进展风险比为0.54；P<0.001），并使缓解率从20%提高至36%（P<0.001）。单纯化疗组和西妥昔单抗组最常见的3级或4级不良事件为贫血（分别为19%和13%）、中性粒细胞减少（23%和22%）和血小板减少（两组均为11%）。西妥昔单抗组9例患者发生脓毒症，单纯化疗组1例患者发生脓毒症（P=0.02）。在接受西妥昔单抗治疗的219例患者中，9%发生3级皮肤反应，3%发生3级或4级输注相关反应。没有与西妥昔单抗相关的死亡。
与单纯铂类化疗加氟尿嘧啶相比，西妥昔单抗联合铂-氟尿嘧啶化疗作为复发性或转移性头颈部鳞状细胞癌患者的一线治疗可改善总生存期。（ClinicalTrials.gov编号，NCT00122460。）
