奥沙利铂、卡培他滨和曲妥珠单抗联合化疗和放化疗在 HER2 阳性胃癌或胃食管交界处癌可切除患者辅助治疗中的 II 期研究（TOXAG 研究）：土耳其肿瘤学会研究。
A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.
机构信息
Department of Medical Oncology, Acibadem Adana Hospital.
Department of Medical Oncology, Hacettepe University.
出版信息
Am J Clin Oncol. 2021 Jul 1;44(7):301-307. doi: 10.1097/COC.0000000000000825.
BACKGROUND
Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated.
METHODS
The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.
RESULTS
Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.
CONCLUSIONS
Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).
背景
曲妥珠单抗联合化疗可延长人表皮生长因子受体 2（HER2）过表达的晚期胃癌患者的总生存期。在这项 II 期开放标签前瞻性研究中，研究了曲妥珠单抗联合化疗和放化疗用于可切除的 HER2 阳性胃腺癌患者的耐受性和安全性。
方法
纳入接受胃切除术加 D2 清扫术的 HER2 阳性胃或胃食管交界处腺癌患者。他们接受 3 个周期奥沙利铂（100mg/m2，静脉注射，第 1 天）加卡培他滨（850mg/m2，口服，第 1 至 14 天），曲妥珠单抗（第 1 周期 8mg/kg，静脉注射，第 1 天，此后 6mg/kg），每 21 天一次，然后进行放化疗。曲妥珠单抗治疗 1 年。
结果
在 212 名筛选的患者中，有 35 名符合条件，34 名接受了治疗。中位年龄为 56 岁（最小到最大：35 至 75 岁），男性患者占 73.5%（n=25），且 33 名（97.1%）为胃腺癌。R0 切除率为 88.2%（n=29）。大多数（26 例，61.7%）处于 III 期疾病。大多数不良事件为 1/2 级，最常见的 3 级副作用为恶心（3 例，8.8%）、呕吐（3 例，8.8%）、腹泻（2 例，5.9%）和体重减轻（n=2，5.9%）。2 例患者在化疗和放化疗的前 3 个周期内死亡；1 例死于肺血栓栓塞，另 1 例死于脑缺血。排除 2 例早期进展和 1 例同意退出后，在其余 31 例患者中，28 例（90.3%）能够完成试验的化疗和放化疗部分。在 25 个月的随访期后，有 21 名患者（61.8%）存活。12 个月和 24 个月的总生存率分别为 75.0%和 58.0%，而 12 个月和 24 个月的无病生存率分别为 65.7%和 55.0%。
结论
曲妥珠单抗联合卡培他滨、奥沙利铂，继以放化疗作为胃或胃食管交界处腺癌的辅助治疗，被认为是安全耐受的。可切除患者中 HER2 过表达的频率与转移性疾病患者相似（试验注册：clinicaltrials.gov 标识符：NCT01748773，2012 年 12 月 13 日，https://clinicaltrials.gov/ct2/show/NCT01748773）。
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