Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

[Successful ventilator weaning by trastuzumab in a HER2-positive breast cancer patient with multiple lung metastases].

We report a case of breast cancer with severe respiratory dysfunction due to multiple lung metastases, which was recovered by treatment with weekly trastuzumab administration. A 47-year-old woman with breast cancer had received a folk remedy from a general practitioner for 4 years. However, she was delivered to a hospital because of severe dyspnea, and intubation was found to be needed and performed. She was diagnosed with left breast cancer with skin and pleural wall invasion, and multiple lung metastases. Pathological examination showed invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive. After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory function improved gradually, and ventilator weaning was successful at 53 days after trastuzumab administration. CT examination also showed a remarkable reduction of lung and lymph node metastases and pleural effusion. She was discharged from our hospital 80 days after treatment, and her treatment with trastuzumab and capecitabine has been ongoing at an outpatient clinic.