Coia L R
Fox Chase Cancer Center, Philadelphia, PA 19111.
Oncology. 1993 Apr;50 Suppl 1:53-60. doi: 10.1159/000227247.
Concurrent administration of chemotherapeutic agents and radiation with or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alone in patients with esophageal cancer. Combinations of 5-fluorouracil (5-FU) and either cisplatin or mitomycin have proven most effective in this setting. As a single agent, mitomycin has generated response rates of 14-42% in patients with squamous cell carcinoma of the esophagus. The response of patients with esophageal adenocarcinoma to single-agent mitomycin is unknown. The clinical use of mitomycin concurrent with 5-FU and radiation is well established in esophageal cancer. There is some experimental evidence to suggest that synergy may occur between 5-FU and mitomycin. Mitomycin is preferentially cytotoxic to hypoxic cells, which are relatively radioresistant. It is not clear whether use of mitomycin with radiation is additive or supra-additive as experimental evidence exists to support both types of interaction. Nonrandomized clinical trials suggest that using either cisplatin or mitomycin concurrently with 5-FU and relatively low-dose radiation (30 Gy) prior to esophagectomy can result in comparable rates of pathologic complete response (20-30%) and median survival (12-19 months). Hematologic toxicity is frequently severe if all 3 drugs are used concurrently in combination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in significant palliation with tolerable morbidity. The use of concurrent chemotherapy and radiation has changed the pattern of failure in esophageal cancer from one dominated by inability to control local disease to one where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this new treatment challenge.
与单纯标准放疗或手术相比，化疗药物与放疗同时使用，无论是否联合手术，在食管癌患者中均能实现更好的局部疾病控制，并延长生存期。已证实，5-氟尿嘧啶（5-FU）与顺铂或丝裂霉素联合使用在这种情况下最为有效。作为单一药物，丝裂霉素在食管鳞状细胞癌患者中的缓解率为14%-42%。食管腺癌患者对单一药物丝裂霉素的反应尚不清楚。丝裂霉素与5-FU及放疗同时使用在食管癌的临床应用中已得到充分确立。有一些实验证据表明，5-FU与丝裂霉素之间可能存在协同作用。丝裂霉素对缺氧细胞具有优先细胞毒性，而缺氧细胞相对具有放射抗性。丝裂霉素与放疗联合使用是相加作用还是超相加作用尚不清楚，因为两种相互作用类型均有实验证据支持。非随机临床试验表明，在食管切除术前，将顺铂或丝裂霉素与5-FU及相对低剂量放疗（30 Gy）同时使用，可产生相当的病理完全缓解率（20%-30%）和中位生存期（12-19个月）。如果三种药物同时与放疗联合使用，血液学毒性通常很严重。在晚期疾病（III期或IV期）患者中，联合化疗/放疗可显著缓解症状，且发病率可耐受。同时使用化疗和放疗已改变了食管癌的失败模式，从以无法控制局部疾病为主转变为以全身衰竭为主。目前和拟进行的食管癌试验也相应地改变了重点，以应对这一新的治疗挑战。
