Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy.

Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease.

Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001).

Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.     

新辅助化疗联合同期放化疗治疗局部晚期鼻咽癌的毒副反应及近期疗效

Background and Objective:Concurrent chemoradiation therapy(CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma(NPC).The effect of neoadjuvant chemotherapy followed by CCRT has not been determined.Therefore,we conducted 2 phase Ⅱ studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel,cisplatin,and 5-fluorouracil(5-Fu)(TPF) followed by radiotherapy and concurrent cisplatin in patients with stage-Ⅲ and -Ⅳ(A -B) NPC.This articl...     

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC.

Between November 1994 and March 1999, 157 patients with Stage IV, M₀ (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35–40 fractions, 1.8–2.0 Gy/fraction/day, 5 days/week, to a total dose 70–72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m² cisplatin, 2,200 mg/m² 5-fluorouracil, and 120 mg/m² leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis.

With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p VALUE = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3).

We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.     

Experience in fractionated stereotactic body radiation therapy boost for newly diagnosed nasopharyngeal carcinoma

PURPOSE: Radiotherapy is the most effective treatment for nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the efficacy and toxicity of fractionated stereotactic body radiation therapy (SBRT) boost for NPC. METHODS AND MATERIALS: Sixty-four patients with newly diagnosed, nonmetastatic NPC were treated with conventional radiotherapy 64.8-68.4 Gy followed by fractionated SBRT boost 12-15 Gy between January 2002 and July 2004. Most patients (72%) presented with Stage III-IV disease. Fifty-two patients also received cisplatin-based concurrent (38) or neoadjuvant (14) chemotherapy. The major endpoints were local control, overall survival, and complications. RESULTS: All patients finished the planned dose of radiotherapy. After a median follow-up of 31 months (range, 22-54), 15 patients developed tumor recurrences--3 in the nasopharynx, 4 in the neck, 5 in distant sites, 1 in both nasopharynx and neck, 2 in the neck and a distant site. The 3-year actuarial rate of local control was 93.1%, regional control 91.4%, freedom from distant metastasis 90.3%, and overall survival 84.9%, respectively. There were no Grade 4 acute or chronic radiation-related complications. CONCLUSIONS: Fractionated SBRT boost for NPC is technically feasible and provides good local control without any severe complications.     

Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma.

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient's head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P =.001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P =.10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P =.66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.     

Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.     

Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma

Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in suboptimal outcome. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. Forty-seven 1997 AJCC Stage II NPC patients were enrolled and analyzed in this prospective phase II clinical trial. The primary tumor and clinically involved nodes received a total dose of 72Gy in 42 fractions. C-Boost for gross disease consisted of 18Gy in 12 fractions commencing on day 19, and delivered at least 6h after the first dose. Patients were assessed for response, survival and toxicity. With a median follow-up of 30 months, 4 patients developed local recurrence only, 2 had persistent neck nodal disease or recurrence, and 1 with both locoregional recurrences. Distant metastases were seen in 5 patients, with or without locoregional recurrence. A total of 5 patients succumbed from nasopharyngeal cancer: four from effects of distant metastases and 1 from progressive local disease. The 3-year local, regional, and overall survival rates were 87.1%, 92%, and 85.9%, respectively. All patients experienced some degree of acute and/or late toxicity. Moderate to severe late toxicities (grade 3 and 4) were observed in 17% of cases. This C-Boost radiotherapy regimen administers a higher biologically effective dose compared with conventional radiation schedules. The local control after C-Boost radiation seems high for patients with stage II nasopharyngeal carcinoma, thus justifies further investigation to confirm its efficacy.     

Ⅲ、Ⅳa期鼻咽癌患者放疗同期化疗加辅助化疗的疗效

背景与目的:较多研究认为放疗前诱导化疗未能提高中晚期鼻咽癌的生存率,对放疗后的辅助化疗能否提高中晚期鼻咽癌的生存率有争议.有作者报道同期放化疗能提高中晚期鼻咽癌患者的疗效.本研究着重探讨放疗同期化疗加辅助化疗治疗Ⅲ、Ⅳa期鼻咽癌的疗效.方法:将80例Ⅲ、Ⅳa期鼻咽癌患者随机分为放疗同期化疗加辅助化疗组(研究组)及单纯放疗组(对照组),每组各40例.研究组于放疗第一周开始使用同期化疗,顺铂25 mg/m2静脉滴注,每周一次,连用6周.辅助化疗于放疗结束后一个月开始,顺铂25 mg/m2,静脉滴注,第1～3天;氟尿嘧啶1000 mg/m2,静脉滴注,第1～3天.每月一次,连用3次.放疗使用常规分割放疗,鼻咽部总剂量70Gy.对照组放疗方法与放疗加化疗组相同,不使用化疗.生存率采用Kaplan-Meier法,生存期的差别比较用log-rank检验,计数资料组间差异用卡方检验.结果:治疗后,研究组和对照组分别有34例和32例鼻咽肿瘤达到CR者(x2=0.35,P＞0.05);颈部淋巴结达到CR者分别为37例和30例(x2=4.50,P＜0.05).研究组1、3、5年生存率分别为92.7%、78.6%、64.2%,对照组1、3、5年生存率分别为81.2%、52.7%、42.3%,两组比较差异有显著性(P＜0.01).研究组1、3、5年无瘤生存率分别为91.2%、76.7%、63.5%,对照组1、3、5年无瘤生存率分别为78.2%、51.9%、40.3%,两组比较差异有显著性(P＜0.01).5年累积远处转移发生率研究组为15.0%,对照组为35.0%,两组比较差异有显著性(x2=4.27,P＜0.05).Ⅲ度口腔粘膜炎发生率研究组为75.0%,对照组为25.0%(x2=20.00,P＜0.01).结论:同期加辅助化疗联合放疗较单纯放疗提高了Ⅲ、Ⅳa期鼻咽癌的颈部淋巴结完全缓解率以及1、3、5年生存率和无瘤生存率,显著降低了远处转移的发生率,但增加了Ⅲ度口腔粘膜炎的发生率.     

Nasopharyngeal carcinoma in childhood and adolescence: a single-institution experience with combined therapy

BACKGROUND: A high cure rate may be attained for locally advanced, undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a combined modality of treatment is employed. Both local and systemic therapies are necessary. Results at a single pediatric institution were analyzed. METHODS: From November 1988 to December 1997, 16 consecutive patients were treated with NPC at the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8-14) years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500 mg/m(2)) plus bleomycin (15 mg/m(2)) daily for 4 days, with cisplatin (100 mg/m(2)) added the last day. External beam radiotherapy was delivered over a median of 52 (range, 45-63) days, to a median cumulative dose to the primary site of 55 (range, 50-61.2) grays (Gy). The median dose for the lower neck area was 45 (range, 45-55.8) Gy. All patients received radiotherapy to the primary site and to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of 7 days per week). RESULTS: The main symptoms at onset were cervical mass (100%), epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV (American Joint Committee on Cancer and International Union Against Cancer TNM system). Complete response was achieved in 45% of patients after initial chemotherapy. With a median follow-up of 63 (range, 23-119) months, disease free survival (with standard error [SE]) and overall survival estimates were 61% (16%) and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or moderate (9%) neck fibrosis were detected at follow-up. CONCLUSIONS: Although this series is small, the authors concluded that NPC patients have a good chance of survival in the setting described, in spite of locally advanced disease. Chemotherapy might be useful in preventing the development of systemic metastases.     

局部晚期鼻咽癌吉西他滨和顺铂联合调强放疗Ⅱ期临床试验

目的 评价吉西他滨和顺铂与调强放疗序贯治疗局部晚期鼻咽癌的疗效和不良反应。方法 71例局部晚期鼻咽癌(Ⅲ期 41例、Ⅳ_A期 30例)患者接受新辅助化疗、调强放疗、辅助化疗,新辅助化疗、辅助化疗各2个疗程\[吉西他滨1000 mg/m²,第1、8天静脉滴注(>30 min);顺铂 25 mg/m²,第 1~3天,静脉滴注;21 d为1个疗程\]。调强放疗鼻咽大体肿瘤体积 66.0~70.4 Gy,颈部淋巴结大体肿瘤体积66 Gy, 临床高危靶体积60 Gy,临床低危靶体积54 Gy。结果 新辅助化疗后的有效率为91.2%,主要急性不良反应为 1~2级骨髓抑制。所有患者随访满 3年,3年鼻咽局部控制率、区域控制率、无远处转移率、总生存率分别为93%、99%、91%、90%。3级晚期不良反应中张口困难 1例、听力下降 2例、颅神经损伤 2例。结论 吉西他滨和顺铂联合调强放疗局部晚期鼻咽癌有效、方便、耐受性良好,值得进一步探索药物最适当的治疗周期。     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.     

Therapeutic results of alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: its usefulness and controversial points

BACKGROUND: The present study was conducted to evaluate the therapeutic results of alternating chemoradiotherapy for locally advanced nasopharyngeal cancer (NPC). METHODS: The subjects consisted of six patients with stage III nasopharyngeal cancer and 26 patients with stage IV nasopharyngeal cancer. Using 6 MV photons, radiotherapy was performed at an exposure of 1.8-2.0 Gy five times per week. That is, a total absorbed dose of 36-40 Gy was irradiated between the base of the skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 26-30 Gy was additionally given thereafter. One course of chemotherapy consisted of the administration of 5-fluorouracil (5-FU) at a dose of 700 mg/m2/24 h for 5 days (days 1-5) and cisplatin (CDDP) at a dose of 50 mg/m2/24 h for 2 days (days 6-7) and a total of 2-3 courses of chemotherapy were performed. During the alternating chemoradiotherapy, chemotherapy was performed initially and 3-5 days after completing the chemotherapy, radiotherapy was performed for 3-4 weeks. Thereafter, chemotherapy and radiotherapy were performed alternately. RESULTS: The scheduled courses of alternating chemoradiotherapy were completed in 30 (94%) of 32 patients. Although one patient developed shock induced by metal allergy to CDDP, no severe adverse effects were noted in any other patients. In these 32 patients, the overall 5-year survival rate was 75% (95% confidence interval: 60-90%) and the progression-free survival rate was 63% (95% CI: 46-89%). CONCLUSIONS: This method of alternating chemoradiotherapy yielded higher or at least similar survival rates and lower toxicities than concurrent chemoradiotherapy and is worth trying in a multi-institutional study.     

Nasopharyngeal cancer in the Middle East: experience of the American University of Beirut Medical Center

PURPOSE: To review the data of nasopharyngeal carcinoma (NPC) treated at the American University of Beirut Medical Center and reflect on the characteristics and treatment outcome of NPC in the Middle East compared with those of Western countries and countries in which NPC is endemic. METHODS AND MATERIALS: Between 1966 and 1998, 151 patients with the diagnosis of NPC received definitive radiotherapy at the American University of Beirut Medical Center. Of the 151 patients, 111 were males (gender ratio, 2.78); the median age was 45 years (range, 11-75 years). Most (95%) patients (n = 144) were Lebanese, 4 were Syrians, and 3 were from the Gulf countries. Most (60%) patients (n = 91) had Stage IV disease, 27% had Stage III, and 13% had Stage I or II disease; nodal disease was present in 117 patients (77%). The pathologic type was predominantly lymphoepithelioma or World Health Organization type III (95 patients, 63%). Treatment consisted of definitive radiotherapy alone for 116 patients (77%). All others received induction chemotherapy, primarily with cisplatin-containing regimens. The median radiation dose was 66 Gy (range, 47-73 Gy) to the primary and 67 Gy (range, 49-85 Gy) to involved neck nodes given at 2 Gy/fraction. The average follow-up was 3.02 years (range, 0.1-24.5 years). RESULTS: The 5-year and 10-year disease-free survival (DFS) rate was 46%. Using univariate analyses, the following factors significantly affected DFS: node size (<3 vs. 3-6 vs. >6 cm; p = 0.01), node level (upper vs. mid vs. lower neck; p = 0.004), and duration of radiotherapy (p = 0.002). However, T stage, age, gender, radiation dose, use of chemotherapy, and histologic features had no statistically significant influence on DFS. The actuarial rate of local control at 5 and 10 years was 81% and 73%. T stage, N stage, and histologic features were statistically significant variables for local control in the univariate analyses. Using a Cox regression model, N stage (N1-N2 vs. N3; relative risk 2.09, p = 0.004) was identified as an independent variable for DFS, and N stage and pathologic features were identified as independent variables for local control. The actuarial rate of distant metastases was 32% at both 5 and 10 years. Distant metastases were only affected by N stage (upper-mid vs. lower neck; p = 0.004). Six patients (4%) were reported to have Grade 4 late complications. CONCLUSION: Our results indicate that the characteristics of NPC patients in Lebanon and their parameters of outcome are comparable to those reported in Western series, particularly for the relative frequency and effect of lymphoepithelial histologic type. Because of potential confounding factors, no definite conclusions about induction chemotherapy could be drawn from this retrospective study.     

局部晚期鼻咽癌放疗与化疗综合治疗的生存分析

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。     

Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy

PURPOSE: To determine the efficacy of chemotherapy adjunctive to radical radiotherapy (neoadjuvant +/- adjuvant) in patients with node-positive nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All the node-positive patients given adjunctive chemotherapy between 1984-1989 (n = 209, CHEMO) were compared with all the node-positive patients treated by radical radiotherapy alone during the same period (n = 409, NCHEMO). The CHEMO group had significantly more bulky nodes, lower cervical/supraclavicular nodes, and more advanced overall stages than the NCHEMO group because nodal size (> or =24 cm) was used as a selection criterion for chemotherapy (1984-1988 departmental protocol and 1988-1989 prospective randomized trial). The chemotherapy consisted of two courses of neoadjuvant cisplatin (100 mg/m2 D1) and 5-fluorouracil (5-FU) (1 gm/m2 D1-D3) in 191 patients. In addition to the two courses of neoadjuvant, four courses of adjuvant chemotherapy, of the same combination, were given after radical radiotherapy in a further 18 patients. Radical radiotherapy delivered a nasopharyngeal dose of 60-62.5 Gy. In addition, parapharyngeal booster external radiotherapy (20 Gy) was given in the presence of parapharyngeal involvement, and intracavitary brachytherapy (24 Gy) was used to treat any local residual tumor diagnosed at 4-6 weeks after external radiotherapy. Both crude and actuarial rates were compared (survival, distant metastases, and local failures) between CHEMO and NCHEMO for all patients, for individual Ho's overall stage, for patients with nodes of different sizes (< or =3 cm, >3-< or =6 cm, >6 cm), for individual T-stage and individual N-stage, and for patients belonging to different gender and different age groups (<40 years, > or =40 years). Multivariate analyses using the Cox Regression Model were performed to identify significant prognostic factors. RESULTS: With a median follow-up of 5.5 years (range 0.7 to 10 years), CHEMO had significantly less local failures overall than NCHEMO; this was especially true for patients with advanced stages (III + IV). Additionally, in all nodal-size subgroups, in all node-positive T3, and in node-positive T3-Stage IV, there was a significant reduction in local failures after chemotherapy. There was a trend toward fewer local failures in favor of chemotherapy in Stage III, Stage IV, and T3-Stage III (0.05相似文献   

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III non-small-cell lung cancer (NSCLC)

PURPOSE: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Treatment consisted of 2 cycles of cisplatin 80 mg/m(2) on Day 1 and vinorelbine 25 mg/m(2) on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. RESULTS: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade > or =3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). CONCLUSION: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed.     

Role of chemoradiotherapy in intermediate prognosis nasopharyngeal carcinoma

To evaluate the long term impact of concurrent chemoradiotherapy (CCRT) compared to radiotherapy (RT) alone in patients with T2N1M0 nasopharyngeal carcinoma (NPC) retrospectively. Three hundred and ninety-two patients with T2N1M0 NPC according to the AJCC 2002 stage classification system were analyzed. Among them, 211 patients were treated with RT alone and the rest of 181 patients were treated with CCRT. A planned dose of 70 Gy was delivered in 2.0 Gy per fraction over 7 weeks to the primary tumor with 6-MV photons or (60)Cobalt γ-ray. The chemotherapy regimen of cisplatin with a dose of 100mg/m(2) was delivered for 2-3 cycles. With a median follow-up of 66 months (range 2.4-117.1 months), the 5-year overall survival (OS) and disease-free survival (DFS) rates was higher in CCRT group compared to RT alone group, though they failed to reach statistical significance (80.2% vs. 76.6%, P=0.778 and 70.5% vs. 64.2%, P=0.413, respectively). A significant improvement was detected in 5-year relapse-free survival (RFS) rate in CCRT group than RT alone group (91.5% vs. 77.3%, P=0.008). Moreover, chemotherapy was the only independent prognostic factor for the 5-year RFS (P=0.007). Concurrent chemoradiotherapy appeared to improve the 5-year RFS rate for patients with T2N1M0 NPC. Large prospective, randomized clinical studies are needed to confirm its therapeutic gain.     

局部晚期鼻咽癌同期放化疗的疗效分析

目的评估同期放化疗方案对局部晚期鼻咽癌患者的疗效、急性毒性反应、依从性和晚期损伤情况。方法74例Ⅲ、Ⅳ期中国人种局部晚期鼻咽癌患者,按照北美Intergroup0099方案接受了同期放疗加辅助化疗的治疗,其急性与晚期毒性反应采用美国放射治疗协作组织（RTOG）的标准进行评价。结果74例患者的5年生存率和无瘤生存率分别为71．3％和43．5％。无5级毒性反应发生,3,4级急性毒性反应主要为造血系统25例,占33．8％;咽部黏膜19例,占25．7％;放疗区皮肤损伤6例,占8．1％。完成放疗、同期放化疗和全部化疗者分别为100．0％、75．7％和47．3％;3—4级晚期并发症主要为唾液腺损伤（17例）、听力损伤（13例）、皮肤及皮下组织损伤（7例）,晚期损伤的5年累积发生率为44．3％。结论与常规放射治疗相比,同期放化疗方案有助于中国人种局部晚期鼻咽癌患者疗效的提高,其急性毒性反应有所增加,晚期损伤基本相同。     

TPF方案诱导化疗加同期顺铂化放疗治疗晚期鼻咽癌的临床研究

 目的　探讨多西紫杉醇（TAX）、顺铂（DDP）、5-氟尿嘧啶（5-Fu）三药联合方案诱导化疗加DDP同期放化疗治疗晚期鼻咽癌的近期疗效及可行性。方法　40例初诊局部晚期（UICC分期Ⅲ、Ⅳ期）鼻咽癌患者入组,随机分为诱导化疗加DDP 3周方案组（A组）,诱导化疗加DDP单周方案组（B组）。两组均先行2个疗程诱导化疗,方案为TAX 60 mg／m2第1天;DDP 60 mg／m2第1天;5-Fu 600 mg／m2 第1天至第5天,每3周重复,共2个周期。第7周开始放疗,放疗第1天同时行化疗。A组：DDP 80 mg／m2第1天,每3周1次,共2次;B组： DDP 30 mg／m2第1天,每周1次,共6次。放疗采用二维适形照射,鼻咽原发病灶68～72 Gy,34～36次,7周,颈部淋巴结阳性区60～66 Gy,30～33次,6～6.5周。结果　40例共完成78个疗程诱导化疗,A、B组各1例出组。38例可评价疗效和不良反应。A组17例完成2个疗程同期DDP化疗;B组10例按计划完成6个周同期化疗,4例完成5周化疗,4例完成4周化疗,1例只完成2周化疗。诱导化疗后CR 4例（10.5 %）,PR 27例（71.1 %）,SD 7例（18.4 %）,总有效（CR+PR）率81.6 %。治疗结束后CR 32例（84.2 %）,PR 5例（13.2 %）,SD 1例（2.6 %）,总有效率 97.4 %。结论　TPF诱导化疗加DDP同期放化疗是治疗晚期鼻咽癌的可行方案,推荐使用同期DDP 3周化疗方案。剂量强度可否提高,有待进一步研究。