紫杉醇联合氟尿嘧啶同期放疗治疗初治局部晚期食管鳞癌患者的Ⅱ期临床研究

Results of a phase Ⅱ study of concurrent 5-fluorouracil/paclitaxel plus radiotherapy in patients with carcinoma of the esophagus

背景与目的:同期放化疗是局部晚期食管癌非手术治疗的标准方案。该研究评价放疗同期紫杉醇联合氟尿嘧啶每周方案化疗对初治局部晚期食管鳞癌患者的疗效及安全性。方法:入组条件为初治局部晚期食管鳞癌患者(T_(2-4)N_(0-1)M_(0-1a)),卡氏评分(KPS)大于等于70,无放化疗禁忌证。治疗方法:调强放疗,61.2 Gy/34次(每天1次1.8 Gy),放疗第1天开始:紫杉醇50 mg/m^2,第1天,联合氟尿嘧啶300 mg/m2连续静脉输注96 h,每周1次,共5次。同期放化疗结束后予以2个疗程巩固化疗:紫杉醇175 mg/m2,第1天,联合氟尿嘧啶1 800 mg/m^2连续静脉输注72 h,每28 d 1次,共2次。研究患者的5年生存率及不良反应。结果:2008年11月—2010年9月共入组50例患者。其中男性38例,女性12例;中位年龄58岁(26~75岁);化疗完成率为72%、放疗完成率为98%;1、2、3和5年生存率分别为75%、56%、42%和28%;血液学毒性中,3度粒细胞缺乏发生率为16%,未出现1例4度粒细胞缺乏及2度以上血小板下降及血红蛋白下降。非血液学毒性中,2度手足麻木、肌肉酸痛、恶心、呕吐及乏力的发生率分别为8%、4%、4%、2%和6%,2度及以上急性放射性食管炎、放射性肺炎及放射性皮肤反应发生率为32%、44%和14%。无一例患者发生4度及以上不良反应。结论:紫杉醇联合氟尿嘧啶每周方案是一种有效的治疗局部晚期食管癌根治性放疗同期化疗方案,该方案的不良反应较轻,安全可靠。

Background and purpose： Concurrent radiochemotherapy is the standard modality for locally advanced esophageal squamous cell carcinoma （ESCC） patients. This clinical trial aimed to assess the effectiveness and toxicity of continuous infusion of 5-fluorouracil （5-FU） and weekly paclitaxel combined with radiotherapy in ESCC patients. Methods： Patients with locally advanced （T2-4N0-1M0-1a） esophageal squamous cell carcinoma were enrolled in a prospective, single-institutional, single-arm study of definitive chemoradiotherapy. Patients received 61.2 Gy with IMRT in 34 fractions. Patients had a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Patients were recommended to receive concurrent 5-FU （300 mg/m2 civ 96 h） for 5 days a week for 5 weeks, plus paclitaxel （50 mg/m2） given during 3 hours every week for 5 weeks. Patients were recommended to receive 2 courses of consolidation chemotherapy after concurrent radio （chemo） therapy （5-FU 1 800 mg/m2 civ 72 h, plus paclitaxel 175 mg/m2 every 28 days）. The primary endpoints of the study were 5 year overall survival and acute toxicity. Results： Fifty patients were enrolled in this study, including 38 male patients and 12 female patients; median age： 58 years （ranged 26 to 75 years）. 72% patients completed all the chemotherapy and 98% patients received the full dose of radiotherapy. 1-, 2-, 3-, and 5- year survival were 75%, 56%, 42% and 28% respectively. Among haematological toxicities, grade 3 leukopenia （16%） was recorded, and no patients experienced any ≥ grade 2 thrombocytopenia or anaemia. Among non-haematological toxicities, the rates of grade 2 peripheral neurotoxicity, arthralgias and myalgias, nausea, vomiting, and fatigue were 8%, 4%, 4%, 2% and 6% respectively. The rates of ≥ grade 2 acute radiation- induced esophageal toxicity, radiation pneumonitis and skin toxicity were 32%, 44% and 14% respectively. No treatment-related deaths occurred and no patients experienced any ≥ grade 4 toxicities. Conclusion： Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy may be an effective and tolerable treatment option for ESCC patients.