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  • br Methods br Results Four patients

    2019-06-12


    Methods
    Results Four patients withdrew from the study due to elevated liver function, allergy to oxaliplatin, refusal of surgery, and refusal of chemotherapy, respectively. The total number of patients included in the final analysis was 31. The patients’ characteristics are presented in Table 1. Most of the patients had Stage III disease (30/31, 96.7%). Median follow-up time was 61.2 months. The resection rate was 64.5% (20/31). Five patients were found with progressive disease (distant buy Oxamflatin including brain, lung, stomach, and bone metastasis). Two patients refused to receive surgery. Three patients were found to have pneumonitis/pneumonia and one patient had elevated liver function. Those who were not fit for operation were scheduled to finish the treatment by definite chemoradiotherapy (adding two cycles of adjuvant chemotherapy). Dose and regimens of adjuvant chemotherapy were cisplatin (20 mg/m2/d) during Days 1–4, with continuous daily oral uracil–tegafur (Ufur) every 3 weeks for two cycles in one patient and epirubicin (50 mg/m2) on Day 1, cisplatin (60 mg/m2) on Day 1, and 5-FU (600 mg/m2/d) during Days 1–4 every 4 weeks for two cycles in one patient. The remaining nine patients did not receive any adjuvant chemotherapy. The pathologic complete response rate was 15% (3/20). The complete resection (R0 resection) rate was 75%. In those patients who did not receive surgery, we used PET/CT scan and gastroendoscopy to evaluate post-CCRT response. The clinical complete response rate was 18% (3/11). Other pathologic findings are presented in Table 2. The overall median survival was 19.3 months (19.95 months with operation; 19.3 months without operation). The 5-year overall survival rate was 37.8% (Fig. 1). The 5-year progression-free survival rate was 31.1% (Fig. 2). There was a significant difference in distant failure-free survival between the patients who did and did not receive surgery (p=0.0298; Fig. 3). No statistical difference was found in the overall survival rate between the patients who did and did not receive the operation (p=0.517; Fig. 4). The acute toxicities (Table 3) were mild, and there were no Grade 3 or above hematologic toxicities. There were no neuropathy toxicities. There was only one patient with Grade 3 esophagus toxicity. Grade 3 lung toxicity occurred in only three patients.
    Discussion The combination of cisplatin and 5-FU is a standard regimen of chemoradiotherapy for esophageal cancer. However, toxicities such as renal insufficiency and bone marrow suppression may lead to an adjustment of the chemotherapy dose or a delayed prescription schedule. To overcome this deadly side effect, the patient must be hydrated with a large amount of water, which will further impact cardiac function. Shinoda et al designed a study to decrease cisplatin and 5-FU dose for reducing toxicity without prejudice to survival. However, the study found there were no differences in toxicities (including hematologic toxicities and esophagitis) in either arm. Furthermore, the lower-dose cisplatin and 5-FU arm did not improve survival. Prior experience of preoperative chemoradiotherapy with oxaliplatin in locally advanced rectal cancer showed that the treatment was well-tolerated and achieved an excellent pathologic complete response. This result demonstrated the role of oxaliplatin as a radiosensitizer. Thus, we investigated preoperative CCRT with oxaliplatin for locally advanced esophageal cancer. To reduce the incidence of distant metastatic disease, recent trials have added additional loading doses of chemotherapy before CCRT. One of the obstacles to adding neoadjuvant chemoradiotherapy is the introduction of systemic toxicity before surgery. The resection rate increased to 73%, and up to 38% of the patients who had surgery achieved a pathologic complete response to the treatment. The locoregional recurrence rate decreased from 29% by surgery alone to 15% by neoadjuvant chemoradiotherapy plus surgery. In this study, the pathologic complete response rate was 15% (3/20) and complete resection (R0 resection) rate was 75%, showing promising results of surgery.