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.

Tea drinking and the risk of esophageal cancer: focus on tea type and drinking temperature.

The association between tea drinking and esophageal cancer is still contradictory. This study is to determine the association between tea drinking and esophageal squamous cell carcinoma focusing on drinking temperature and tea types. A population-based case-control study was conducted in a high esophageal squamous cell carcinoma risk area in China. A total of 942 incident esophageal squamous cell carcinoma cases with historical confirmation and 942 age- and sex- individually matched community controls were recruited from the study area. Trained interviewers using a structured questionnaire collected detailed information on tea drinking, diet, smoking and alcohol drinking habits. Habitual tea drinking temperature was measured with a thermometer during interviews. We analyzed the association between tea consumption, drinking temperature and esophageal squamous cell carcinoma, stratified by tea type, while adjusting for other potentially confounding factors. Drinking very hot tea (>65°C) was significantly associated with the increased risk of esophageal squamous cell carcinoma (odds ratio = 1.67, 95% confidential interval 1.25-2.24) relative to non-drinkers. Consumption of black tea, irrespective of the frequency, intensity and tea leaf amount, was significantly associated with a higher risk (P for trend <0.01). Compared to those who consumed <300 g/month tea leaves at ≤65°C, those who consumed more than 300 g/month tea leave at >65°C had a more than 1.8-fold higher risk of esophageal squamous cell carcinoma for both green tea and black tea. Our results provide more evidence that drinking very hot tea (above 65°C) are significantly associated with an increased risk of esophageal squamous cell carcinoma.

Investigating tea temperature and content as risk factors for esophageal cancer in an endemic region of Western Kenya: Validation of a questionnaire and analysis of polycyclic aromatic hydrocarbon content.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is common in certain areas worldwide. One area, western Kenya, has a high risk of ESCC, including many young cases (<30 years old), but has limited prior study of potential risk factors. Thermal injury from hot food and beverages and exposure to polycyclic aromatic hydrocarbons (PAHs) have been proposed as important risk factors for ESCC in other settings. The beverage of choice in western Kenya is milky tea (chai). METHODS: Healthy individuals >18 years of age who were accompanying relatives to an endoscopy unit were recruited to participate. The preferred initial temperature of chai consumption in these adults was measured by questionnaire and digital thermometer. Comparisons of these results were assessed by kappa statistics. Concentrations of 26 selected PAHs were determined by gas chromatography/mass spectrometry in samples of 11 brands of commercial tea leaves commonly consumed in Kenya. RESULTS: Kappa values demonstrated moderate agreement between questionnaire responses and measured temperatures. The mean preferred chai temperatures were 72.1 °C overall, 72.6 °C in men (n = 78), and 70.2 °C in women (n = 22; p < 0.05). Chai temperature did not significantly differ by age or ethnic group. The PAH levels in the commercial Kenyan tea leaves were uniformly low (total PAH < 300 ng/g of leaves). CONCLUSIONS: Study participants drink chai at higher temperatures than previously reported in other high-risk ESCC regions. Chai is not, however, a source of significant PAH exposure. Very hot chai consumption should be further evaluated as a risk factor for ESCC in Kenya with the proposed questionnaire.