局部晚期鼻咽癌放疗与化疗综合治疗的生存分析

Induction chemotherapy followed by radiotherapy and adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma treated

目的探讨局部晚期鼻咽癌放化综合治疗疗效和毒副反应。方法回顾性分析77例经病理证实鼻咽癌患者。年龄17～74岁,男:女=3.8:1。1992年福州分期T1、12、T3、T4期分别为11、33、22、11例,N0、N1、N2、N3期分别为7、15、44、11例。临床分期Ⅲ期56例,ⅣA期21例。所有患者放疗前接受诱导化疗1～3个疗程:顺铂20 mg/m^2,氟尿嘧啶500 mg/m^2,其中62例应用甲酰四氢叶酸钙100 mg/m^2,均为第1～3天,2周后重复。化疗结束后2周内放疗:鼻咽原发病灶均采用^(60)Co照射1.8～2.0 Gy/次,总剂量64～78 Gy;57例采用面颈联合野+耳前野+鼻前野治疗,20例采用耳前野+鼻前野照射,9例采用耳后野加量6～8 Gy分3～4次,13例给予颅底小野补量4～8 Gy分2～4次;颈部放射源用^(60)Co、180 kV X线和9 MeV电子束,N0期患者仅照射上颈部,有颈部转移者照射全颈,预防剂量50～55 Gy,根治剂量60～68 Gy;1例外照射结束后因鼻咽腔内肿瘤残留,给予后装治疗2次,间隔1周,10 Gy/次)。放疗结束后3周给予辅助化疗:顺铂20 mg/m^2,氟尿嘧啶500 mg/m^2,甲酰四氢叶酸钙100 mg/m^2,均为第1～3天,3周后重复,共2～4疗程。结果中位随访60个月,5年总生存率、无瘤生存率、无复发生存率、无远处转移生存率分别为68%、58%、81、75%。≥4个化疗周期与≤3个化疗周期生存曲线比较差异无统计学意义(X^2=0.05,P=0.831)。主要急性反应有血液学毒性:1级11例,2级7例,3级2例;黏膜炎:2级33例,3级20例,4级1例;消化道反应:1级21例,2级11例,3级1例;皮肤反应:2级30例,3级4例。晚期损伤:1例发生放射性脑损伤,无其他颅神经损伤发生;张口困难轻度4例,中度1例;听力减退轻度31例,中度7例,严重1例。化疗周期≥4个与≤3个的听力损伤差异有统计学意义(z=2.06,P=0.039)。绝大多数放疗结束后都有程度不等的口干,随访中都明显好转,至末次随访时轻度口干13例,中度3例。结论以顺铂和氟尿嘧啶为基础的诱导化疗+放疗+辅助化疗局部晚期鼻咽癌的疗效较单纯放疗无明显提高,但可能加重患者听力的晚期损伤。

Objective To summarize the efficacy and toxicities of induction chemotherapy followed by radiotherapy and adjuvant chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma （NPC）. Methods From Oct. 1997 to Nov. 2000, 77 patients with histologically proven locally advanced NPC, staged according to the Fuzhou stage classification, were retrospectively studied. Before radical radiotherapy, the patients received 1-3 cycles cisplatin（PDD） 20 mg/m^2 on Days 1-3 and fluorouracil（5-Fu） 500 mg/m^2 on Days 1-3 repeated every two weeks. Sixty-two patients also received calcium folinate（CF） 100 mg/m^2 on Days 1-3. Two to four cycles of adjuvant chemotherapy was given 21 days after the completion of radiotherapy. All patients received radical radiotherapy by ^60Co to the nasopharynx and neck with a total dose of 64-78 Gy at 1.8-2.0 Gy per fraction over 7.0-7. 5 weeks to the primary site. The dose to the lymph nodes was 60-68 Gy. After-loading radiotherapy was given to the residual disease in 1 patient （20 Gy in 2 fractions）. Results The median follow-up was 60 months （ranged from 3 to 103 months）. The 5-year overall survival rate （OS） , disease- free survival rate （DFS）, relapse-free survival rate （RFS） and distant metastasis-free survival rate （DMSF） were 68% , 58% , 81% and 75%. The patients who received more than 3 cycles of chemotherapy or not had no significant effects on the OS （ x^2 =0.05 ,P =0. 831 ）. The incidence of grade 3 or 4 acute side-effects of radiotherapy was vomiting 1% , leukopenia 3% , mucositis 23% and skin reaction 5% , all of which eventually resolved. The most frequent late toxicities were hearing impairment （51%）. Patients with more than 3 cycles chemotherapy were more likely to have late hearing loss （z = 2.06, P = 0. 039）. Only one patient had radiation-induced brain damage. Conclusions Induction chemotherapy, radiotherapy and adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma would result in a comparable outcome, but may impair the hearing of patients.