Lancet. 1996 Oct 19;348(9034):1049-54.
Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has, in uncontrolled studies, yielded similar local tumour control and survival rates to surgery. However, whether the addition of chemotherapy improves outcome without adding to morbidity is not known. Our trial was designed to compare combined modality therapy (CMT) with radiotherapy alone in patients with epidermoid anal cancer.
From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 weeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m2 for 4 days or 750 mg/m2 for 5 days) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin (12 mg/m2) on day 1 of the first course (295 patients). We assessed clinical response 6 weeks after initial treatment: good responders were recommended for boost radiotherapy and poor responders for salvage surgery. The main endpoint was local-failure rate (> or = 6 weeks after initial treatment); secondary endpoints were overall and cause-specific survival. Analysis was by intention-to-treat.
In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after initial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local failure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduction in the risk of local failure in the patients receiving CMT (relative risk 0.54, 95% CI 0.42-0.69, p < 0.0001). The risk of death from anal cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p = 0.02). There was no overall survival advantage (0.86, 0.67-1.11, p = 0.25). Early morbidity was significantly more frequent in the CMT arm (p = 0.03), but late morbidity occurred at similar rates.
Our trial shows that the standard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved for those who fall on this regimen.
在非对照研究中，单独放疗或放疗联合化疗对肛管癌进行非手术治疗，其局部肿瘤控制率和生存率与手术治疗相似。然而，化疗的加入在不增加发病率的情况下是否能改善预后尚不清楚。我们的试验旨在比较联合放化疗（CMT）与单纯放疗对表皮样肛管癌患者的疗效。
在856例考虑纳入我们多中心试验的患者中，585例患者被随机分组，一组在4 - 5周内分20或25次接受45 Gy放疗（290例患者），另一组在放疗的第一周和最后一周通过持续输注接受相同放疗方案联合5-氟尿嘧啶（4天，1000 mg/m² 或5天，750 mg/m²），并在第一疗程的第1天接受丝裂霉素（12 mg/m²）（295例患者）。初始治疗6周后评估临床反应：反应良好者建议接受强化放疗，反应不佳者建议接受挽救性手术。主要终点是局部失败率（初始治疗后≥6周）；次要终点是总生存率和病因特异性生存率。分析采用意向性分析。
在单纯放疗组和CMT组中，分别有5例和3例不符合纳入标准，初始治疗6周后分别有6例和9例死亡。中位随访42个月（四分位间距28 - 62个月）后，279例放疗患者中有164例（59%）出现局部失败，而283例CMT患者中有101例（36%）出现局部失败。这使得接受CMT治疗的患者局部失败风险降低了46%（相对风险0.54，95%可信区间0.42 - 0.69，p < 0.0001）。CMT组肛管癌死亡风险也有所降低（0.71，0.53 - 0.95，p = 0.02）。总生存率无优势（0.86，0.67 - 1.11，p = 0.25）。CMT组早期发病率明显更高（p = 0.03），但晚期发病率相似。
我们的试验表明，大多数表皮样肛管癌患者的标准治疗应是放疗联合输注5-氟尿嘧啶和丝裂霉素，手术仅适用于对该方案治疗效果不佳的患者。
