Lokich J J, Shea M, Chaffey J
Cancer. 1987 Aug 1;60(3):275-9. doi: 10.1002/1097-0142(19870801)60:3<275::aid-cncr2820600302>3.0.co;2-r.
Thirteen patients with esophageal or gastroesophageal tumors with regional disease only were treated with sequential combined therapy. Weeks 1 to 6 continuous (24 hours) infusion 5-fluorouracil (5-FU) 300 mg/m2/d; weeks 6 to 10 or 12 infusional 5-FU administered concomitantly with radiation to the primary tumor site using standard fractionation with a cumulative median dose of 5000 rad; range 4400 to 6900 rad. Surgery was performed in five patients. All patients were evaluable for assessing response to the initial 5-FU infusion and 11/13 patients demonstrated tumor regression. Of 12 evaluable patients subsequently receiving combined infusional 5-FU and concomitant radiation, all 12 achieved complete clinical (10) or pathologic (two) tumor regression. Two of five patients having surgical resection had no pathologic evidence of tumor. All patients had relief of dysphagia within 1 week of initiating chemotherapy. Acute complications of therapy included stomatitis (two patients); hand-foot syndrome (two patients), and subclavian vein thrombosis (two patients). Stricture requiring periodic dilation occurred in three patients, and one patient developed a tracheoesophageal fistula at 36 months. Local control was maintained in 12/13 evaluable patients. Four of 13 patients were alive and without disease at 12 to 46 months. Nine patients died of distant metastases at 6 to 40 months. Median survival for the whole group was 16 months. Ten of the 13 patients (77%) survived for more than 1 year and 3/13 (22%) survived more than 3 years. This pilot study demonstrates the activity of 5-FU administered on an infusion schedule in both squamous and adenocarcinoma of the esophagus and the capacity to deliver infusional 5-FU throughout standard fractionation radiation. The local control and survival data may provide a basis for expanded Phase II trials, and a comparative trial against surgery alone might also be justified.
13例仅患有局部病变的食管或胃食管肿瘤患者接受了序贯联合治疗。第1至6周持续（24小时）输注5-氟尿嘧啶（5-FU）300mg/m²/天；第6至10周或12周，5-FU输注与对原发肿瘤部位进行的放疗同时进行，采用标准分次放疗，累积中位剂量为5000拉德；范围为4400至6900拉德。5例患者接受了手术。所有患者均可评估对初始5-FU输注的反应，13例患者中有11例出现肿瘤消退。在随后接受5-FU输注联合放疗的12例可评估患者中，所有12例均实现了临床完全缓解（10例）或病理完全缓解（2例）。接受手术切除的5例患者中有2例没有肿瘤的病理证据。所有患者在开始化疗后1周内吞咽困难均得到缓解。治疗的急性并发症包括口腔炎（2例患者）；手足综合征（2例患者）和锁骨下静脉血栓形成（2例患者）。3例患者出现需要定期扩张的狭窄，1例患者在36个月时发生气管食管瘘。13例可评估患者中有12例维持了局部控制。13例患者中有4例在12至46个月时存活且无疾病。9例患者在6至40个月时死于远处转移。整个组的中位生存期为16个月。13例患者中有10例（77%）存活超过1年，3/13（22%）存活超过3年。这项初步研究证明了按输注方案给予5-FU在食管鳞状细胞癌和腺癌中的活性，以及在整个标准分次放疗过程中给予5-FU输注的能力。局部控制和生存数据可能为扩大的II期试验提供基础，与单纯手术的对比试验也可能是合理的。
