A Phase II Study with Lead‐In Safety Cohort of 5‐Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2‐Positive Esophagogastric Adenocarcinomas

Lessons Learned Neoadjuvant 5‐fluorouracil, oxaliplatin, and lapatinib in combination with radiation therapy is safe for neoadjuvant treatment for patients with localized human epidermal growth receptor 2‐positive esophagogastric adenocarcinoma. Evaluation of this drug combination in a larger patient pool would allow for more accurate analysis of its efficacy. Background The optimal design of neoadjuvant chemoradiation for the treatment of localized esophagogastric cancers is the subject of much debate. In this nonrandomized trial, we evaluated neoadjuvant 5‐fluorouracil (5‐FU), oxaliplatin, and lapatinib in combination with radiation therapy as neoadjuvant treatment for patients with localized human epidermal growth receptor 2 (HER2)‐positive esophagogastric adenocarcinomas. Methods Patients received neoadjuvant 5‐FU (225 mg/m2 continuous intravenous infusion, days 1–42), oxaliplatin (85 mg/m2 intravenously [IV], days 1, 15, and 29), and lapatinib (six patients, 1,000 mg p.o., days 1–42; six patients, 750 mg p.o., days 1–42) plus radiation (1.8 Gy/day Monday through Friday for 50.4 Gy total). Following restaging, eligible patients underwent definitive resection, and pathologic response to neoadjuvant therapy was assessed. Planned enrollment was 42 patients. The primary endpoint was the pathologic complete response (pCR) rate. Results Twelve patients (median age 64 years; 67% male) received a median of 5.6 weeks of treatment (range: 1.1–8.4). The pCR rate was 8%; four of the 12 patients underwent tumor resection and one patient had a pCR, with pathologic partial response in the remaining three. The most common lapatinib‐related adverse events included (all grades) nausea (67%) and diarrhea (58%), although these were all grade 1 or 2. Enrollment was halted due to low accrual. Conclusion The treatment regimen was determined to be safe. The study was terminated early due to low accrual. 经验总结 • 5‐氟尿嘧啶（5‐FU）、奥沙利铂和拉帕替尼联合放疗的新辅助疗法用于局部人表皮生长受体2阳性食管胃交界处腺癌患者是安全的。 • 在更大的患者库中评估该药物组合将能够更准确地分析其疗效。 摘要 背景.用于治疗局部食管胃交界处癌的最佳设计的新辅助放化疗方法存在很多争论。在这项非随机试验中, 我们评估了用于局部人表皮生长受体2（HER2）阳性食管胃交界处腺癌患者的5‐氟尿嘧啶（5‐FU）、奥沙利铂和拉帕替尼联合放疗的新辅助疗法。 方法.患者接受了新辅助疗法, 包括5‐FU（225 mg/m2, 连续静脉滴注, 第1‐42天）、奥沙利铂 [85 mg/m2, 静脉滴注（IV）, 第1、15和29天]和拉帕替尼（6例患者, 1 000 mg po, 第1‐42天；6例患者, 750 mg po, 第1‐42天）联合放疗（1.8 Gy/天, 周一至周五, 共50.4 Gy）。重新分期后, 符合条件的患者接受了根治术, 并评估了对新辅助治疗的病理反应。计划入组42例患者。主要终点是病理完全缓解（pCR）率。 结果.12例患者（中位年龄为64岁；男性占67％）接受治疗的中位周数为5.6（范围为 1.1‐8.4）。pCR率为8％; 12例患者中有4例接受了肿瘤切除术, 其中1例患者获得pCR, 其余三例患者获得病理部分缓解。最常见的与拉帕替尼有关的不良