紫杉醇、卡铂和西妥昔单抗联合治疗作为复发性和/或转移性头颈部鳞状细胞癌（CSPOR-HN02）一线治疗的 II 期临床试验。

Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

机构信息

Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan.

出版信息

Ann Oncol. 2018 Apr 1;29(4):1004-1009. doi: 10.1093/annonc/mdy040.

DOI:10.1093/annonc/mdy040

PMID:29408977

Abstract

BACKGROUND

The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN.

PATIENTS AND METHODS

Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients.

RESULTS

Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia.

CONCLUSIONS

The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population.

REGISTERED CLINICAL TRIAL NUMBER

UMIN000010507.

摘要

背景

铂类、5-FU 和西妥昔单抗（PFE）联合治疗是复发性和/或转移性头颈部鳞状细胞癌（R/M SCCHN）的一线治疗标准。然而，该方案需要住院治疗以确保适当的水化和 5-FU 的持续输注，并导致严重的恶心和厌食。我们评估了紫杉醇、卡铂和西妥昔单抗（PCE）作为 R/M SCCHN 患者一线治疗的疗效和安全性。

患者和方法

入选标准包括复发性和/或转移性、组织学证实的口咽、口腔、下咽或喉鳞状细胞癌；PS 0-1；有足够的器官功能；R/M SCCHN 无合适的局部治疗；且无 R/M SCCHN 的既往全身化疗。化疗包括紫杉醇 100mg/m2，第 1、8 天；卡铂血药浓度-时间曲线下面积 2.5，第 1、8 天，每 3 周重复，最多 6 个周期；西妥昔单抗初始剂量为 400mg/m2，然后每周 250mg/m2，直至疾病进展或出现不可耐受的毒性。主要终点是总缓解率。次要终点是安全性、治疗完成率、无进展生存期、总生存期和临床获益率。计划样本量为 45 例。

结果

2013 年 7 月至 2014 年 10 月共入组 47 例患者。45 例可评估患者中，40 例为男性；中位年龄为 63 岁；东部肿瘤协作组体力状况为 0/1 分的分别有 23/22 例；部位为下咽/口咽/口腔/喉的分别有 17/11/10/7 例；36/9 例分别为吸烟者/不吸烟者。总缓解率，主要终点，为 40%。中位总生存期为 14.7 个月，无进展生存期为 5.2 个月。3/4 级不良事件包括中性粒细胞减少（68%）、皮肤反应（15%）、乏力（9%）和发热性中性粒细胞减少（9%）。一例肠道肺炎患者发生了潜在治疗相关的死亡。