Efficacy and feasibility of cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma

OBJECTIVE: To investigate the efficacy and feasibility of a cisplatin-based concurrent chemoradiotherapy (CRT) protocol based on Intergroup Study 0099 for nasopharyngeal carcinoma (NPC). METHODS: Sixteen patients with stage II-IVB NPC were treated with a protocol of cisplatin-based concurrent CRT and adjuvant chemotherapy from 1998 to 2002. Three courses of cisplatin (80 mg/m2) were scheduled during 70 Gy of radiotherapy (RT), and two agents of adjuvant chemotherapy (FP regimen: cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day by 4-day continuous infusion) were challenged. Overall survival (OS) and relapse-free survival (RFS) rates were calculated by the Kaplan-Meier method. RESULTS: Median follow-up duration was 45 months. Both 3-year OS and RFS rates were 81%. Proportions of patients who tolerated each scheduled treatment were 94% for RT, 63% for concurrent chemotherapy and 38% for adjuvant chemotherapy. CONCLUSIONS: Our protocol of the cisplatin-based concurrent CRT followed by adjuvant chemotherapy consisting of FP regimen was effective for Japanese patients with NPC. However, the doses and numbers of cycle of chemotherapy need to be modified because of the low compliance rate. Larger numbers of data accumulation and/or multi-institutional trials may be warranted to confirm the efficacy of this protocol.     

奈达铂联合紫杉醇和顺铂联合紫杉醇同步放化疗局部晚期鼻咽癌的临床随机对照实验

目的 通过临床随机对照实验观察奈达铂是否能够替代顺铂与紫杉醇联合同步放化疗局部晚期鼻咽癌,是否能够提高治疗的耐受性.方法 实验组(TN组)30例,采用紫杉醇135 mg/m2ivgtt d1+奈达铂10 mg/m2 ivgttd1诱导化疗,每3周为1个化疗周期,共2个疗程,以后行同样方案同期放化疗,仍然每3周为1个化疗...     

Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study.

BACKGROUND: To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. RESULTS: There were nine complete responses and 23 partial responses in the 44 patients, achieving an overall response rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. CONCLUSIONS: Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.     

奈达铂联合放疗治疗晚期鼻咽癌

背景与目的：鼻咽癌的标准治疗方法是放射治疗,但超过70%的患者确诊时已到晚期,单纯放疗后的局部复发率及远处转移率较高.放疗联合应用化疗可显著改善晚期鼻咽癌的疗效.因此本研究放疗联合含奈达铂（nedaplatin,NDP）化疗方案的新辅助化疗治疗晚期鼻咽癌的近期疗效和不良反应,以含顺铂（cisplatin,DDP）化疗方案作为对照组.方法：64例晚期鼻咽癌患者,随机分成奈达铂治疗组32例,顺铂对照治疗组32例.两组均在诱导化疗2个周期后行放射治疗.化疗方案：NDP 80 ms/m2,静滴,第1天,氟尿嘧啶（5-Fu）500 mg/m^2,静滴,第1～5天;DDP 40 mg/d,静滴,第1-3天,5-Fu 500 mg/m^2,静滴,第1-5天.放射治疗鼻咽部（7～9周）总剂量：66～74 Gy/（33～37）次;颈部淋巴结每（7～8.5周）总剂量：（60～70） Gy/（30～35）次;颈部预防剂量：（48～50）Gy.结果：NDP组有效率（56.25%）,DDP组有效率（50.00%）,差异无显著性（P＞0.05）;NDP组呕吐发生率（15.62%）显著低于DDP组（46.88%）（P＜0.01）;两组肾脏毒性差异无显著性;两组白细胞下降发生率分别为62.50%和56.25%,差异无显著性（P＞0.05）;血小板下降发生率NDP组（59.38%）较DDP组（31.25%）高,差异有显著性（P＜0.05）.结论：NDP治疗晚期鼻咽癌近期疗效与DDP相近,但NDP有较少的胃肠道反应发生,其毒副反应主要是骨髓抑制所致的血小板减少.     

中晚期鼻咽癌同期放化疗的临床研究

目的：探讨同期化疗加放疗对中晚期鼻咽癌远期疗效的影响。方法：８８例３、４ａ期鼻咽癌（＇９２分期）随机分为化疗加放疗组（７和化组４４例）和单纯放疗组（单放组４４例）。单纯组采用＾６０Ｃｏ加１８０ｋｖＸ线常规分割，鼻咽部及颈切线用＾６０Ｃｏ－γ线，颈部垂直野用１８０ｋｖＸ射线。鼻咽部剂量６５～７８Ｇｙ，颈部根治量６０～７０Ｇｙ，残留病灶加１０Ｇｙ左右，放化组加用顺铂（ＤＤＰ）及氟尿嘧啶（５－ＦＵ）化疗     

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study.

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m(-2), doxorubicin 40 mg m(-2) and cisplatin 60 mg m(-2) were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m(-2) and leucovorin 30 mg m(-2) for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9-100%) with a complete response rate (CR) of 6% (95% CI: 0-15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7-44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8-91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6+/-0.4 and 18.1+/-3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6-41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox's multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study.     

中晚期鼻咽癌新辅助化疗联合放疗的临床研究

目的:探讨新辅助化疗联合放疗治疗中晚期鼻咽癌的疗效。方法:自1998年1月至2002年11月,92例中晚期鼻咽癌患者分别采用新辅助化疗联合放疗(化放组)及单纯放疗(单放组)。新辅助化疗组在放疗前给予DDP 5-Fu化疗2周期,二组放疗相同。鼻咽DT(68~72)Gy/(7~7.5)W,颈部50Gy~76Gy/(5~8)W,比较二组疗效及不良反应。结果:放疗结束时鼻咽肿瘤完全退缩率二组分别为60.4%,38.6%(P<0.05),颈部淋巴结完全退缩66.7%,36.4%(P<0.05),急性反应化放组的胃肠道反应,白细胞下降等副反应增加。1年生存率化放组及单放组分别为81.3%,81.8%(P>0.05),3年生存率分别为58.3%,61.3%(P>0.05)。结论:新辅助化疗联合放疗治疗中晚期鼻咽癌能提高近期鼻咽病灶及颈淋巴结完全消退率,未能提高中晚期病人的生存率,未能降低远处转移的几率。     

鼻咽癌调强放疗中肿瘤和正常组织体积-剂量变化的研究

目的:研究鼻咽癌在调强放射治疗过程中,肿瘤和正常组织的体积、形态变化对各自剂量受量的影响。方法:2009年1月-2010年6月间初诊经病理明确诊断的鼻咽癌患者42例,所有患者经头颈肩膜固定行模拟CT,在CT图像上逐层勾画治疗靶区和正常组织,采用6MV X线9野共面调强放射治疗计划（IMRT）。鼻咽原发灶及颈部转移淋巴结照射剂量66Gy/30f/6w,鼻咽部和颈部淋巴引流区亚临床病灶照射剂量60Gy/30f/6w。治疗设备为西门子ONCOR直线加速器。治疗期间每日采集患者治疗体位0度和90度正交二维摄片图像,同原始计划DRR图像对比,在三维方向对患者进行摆位误差校正,然后实施放射治疗。每周采集一次患者治疗体位头颈部CT图像,把治疗计划按照标记点移植到每周CT上,重新进行计量计算,分析患者在治疗期间靶区及正常组织剂量分布变化。同步化疗采用多西他赛加顺铂方案,每三周一次,在放疗开始前1周内开始同步治疗。结果:所有患者放疗前GTV1平均体积39.19cc,GTV2平均体积16.59cc,放疗第4周及第6周GTV1平均退缩分别为26.41%、62.68%,GTV2平均退缩分别为28.43%、53.93%。治疗前双侧腮腺体积平均为24.16cc,放射治疗第4周,平均腮腺体积为19.04cc,第6周平均腮腺体积为17.54cc。正常组织计量受量方面,脊髓（D1%）、脑干（D1%）、颞叶（D1%）、内耳（Dmean）、腮腺（V30）,原计划计量分别为:（41.2±0.98）Gy、（51.26±1.57）Gy、（59.95±2.11）Gy、（45.02±1.98）Gy、（47.87±18.05）%。照射第4周分别为:（44.09±1.88）Gy、（52.81±2.47）Gy、（62.04±2.43）Gy、（47.24±3.68）Gy、（49.03±15.68）%。第六周（44.44±2.7）Gy、（54.14±2.51）Gy、（62.34±2.86）Gy、（48.37±5.37）Gy、（52.19±15.51）%。结论:随着鼻咽癌调强放射治疗的进行,照射肿瘤靶区同原始计划剂量分布会有一定差异,除1例淋巴结退缩及病人消瘦等原因而造成外轮廓内收较大的患者以外,其余CTV实际照射剂量为处方剂量95%以上。正常组织在整个治疗过程所受照射剂量同原始计划比较有所增加。     

鼻咽癌的局部免疫治疗

目的研究鼻咽癌患者的免疫功能状况和免疫治疗效果。方法检测了23例鼻咽癌患者外周血的NK细胞,IL-2、TNF-α和T淋巴细胞亚群的浓度水平,并与20例健康人作对比。用rIL-2对13例患者进行局部免疫治疗。10例患者进行全身免疫治疗。结果治疗前鼻咽癌患者的TNF-α浓度水平与健康人相比,差别有非常显著的意义。IL-2的差别有显著的意义。而用rIL-2治疗前后,患者各项免疫指标比较差别均无显著意义。临床治疗效果,局部治疗部分缓解(PR)5例(5/13)不变7例(NC),恶化的1例(PD)。全身用药患者的精神状况,体力有改善。但肿瘤的大小未见明显变化。结论rIL-2局部应用于鼻咽癌有一定的疗效。     

调强放疗同期联合每周奈达铂治疗局部晚期鼻咽癌的临床研究

目的：观察调强放疗同期联合每周奈达铂治疗局部晚期鼻咽癌的疗效以及不良反应。方法：38例局部晚期鼻咽癌患者进入分析。所有患者均接受调强放疗。鼻咽肿瘤体积（ GTV）处方剂70Gy,颈部转移淋巴结（GTVnd）70Gy,临床靶体积1（CTV1）66Gy,临床靶体积2（CTV2）54Gy。于放疗第1周起静脉滴注奈达铂30mg/m2,每周1次,连用7周。结果：38例患者均可评价毒副反应及客观疗效。所有患者均完成了同期放化疗,少见严重不良反应。中位随访38个月,全组1、2、3年总生存率分别为94.7％、84.2％、78.9％,1、2、3年局部/区域控制率分别为100％、94.7％、92.1％,1、2、3年无远处转移生存率分别为97.3％、94.7％、73.6％。结论：调强放疗同期联合每周奈达铂治疗局部晚期鼻咽癌病人可达到较高的局部控制率和生存率,不良反应可耐受。     

GP和FP治疗转移性鼻咽癌的疗效观察

目的：观察吉西他滨＋顺铂（GP）方案和氟尿嘧啶＋顺铂（FP）方案治疗晚期复发转移性鼻咽癌的疗效及不良反应。方法：选择放疗后复发转移性鼻咽癌60例,分别采用GP方案或FP方案静脉化疗,21天为1周期。结果：GP组：CR5例、PR19例,有效率（CR＋PR）80％;FP组：CR2例、PR14例,有效率（CR＋PR）53．3％两组有效率有显著差异（P=0．0283）。中位PFS（无进展生存期）GP组8个月,FP组3个月（P=0．0001）。中位OS期（总生存期）GP组11个月,FP组7个月（P=0．0002）。两组毒性均能耐受。结论：GP方案较FP可以更好改善复发转移性鼻咽癌的RR、PFS和OS。     

Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile ({"type":"entrez-geo","attrs":{"text":"GSE12452","term_id":"12452"}}GSE12452 and {"type":"entrez-geo","attrs":{"text":"GSE68799","term_id":"68799"}}GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.     

中晚期鼻咽癌新辅助化疗联合放疗的临床研究

目的　观察不同新辅助化疗方案联合放疗在局部晚期鼻咽癌的疗效及毒副反应。评价含HD DDP方案的临床可行性。方法　 10 0例局部晚期鼻咽癌患者随机分为单纯放射治疗组 46例 (A组 ) ,低剂量新辅助化疗组 2 8例 (B组 ) ,含HD DDP新辅助化疗组 2 6例 (C组 )。化疗方案 :B组DDP总量 10 0～ 12 0mg/ 3～ 5天 ,5 FU 5 0 0～ 75 0mg/天 ,共 5天 ;C组DDP 10 0～ 13 0mg/天 ,第一天用 ,同时水化利尿 2天 ,5 FU剂量同B组 ,B、C组还分别加用ADM、PYM、VCR、MTX、Me CCNU其中之一 ,2 1天为一周期 ,共用 2～ 3周期 ,化疗后 10～ 14天放疗。常规放射治疗 :鼻咽原发灶DT66～80Gy/ 6.5～ 8周 ,颈部转移灶DT60～ 70Gy/ 6～ 7周 ,颈部预防量DT5 0Gy。 结果　所有病例如期完成治疗。放疗 40Gy时 ,颈部转移灶消退率综合组高于单纯放疗组 (C、B、A组分别为 73 .0 7%、64 .2 8%、5 4.3 5 % )。结束时、结束 1～ 2个月后 ,综合组尤其HD DDP组颈部转移灶完全缓解率明显高于单纯放疗组 (C、B、A组分别为 10 0 %、92 .86%、82 .61% )。鼻咽原发灶缓解率亦有提高 (C、B、A组分别为 88.46%、78.5 7%、68.5 7% )。毒性反应主要表现是综合组较单纯放疗组更高的胃肠道反应及 1～ 3级骨髓抑制和脱发 ,B、C组无明显差别 ,无一例肾功能不     

Familial nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has a striking geographical and ethnical distribution. It occurs with high frequency in southern China and Southeast Asia. Family clustering was also observed in NPC and a typical family with 15 NPC cases was introduced in this paper. Epidemiological and genetic studies have been carried out in the previous decades and vast information was accumulated for familiar NPC, in terms of risk factors, inheritance mode, and involvement of gene polymorphisms. The major findings in this field were summarized. Furthermore, future directions leading to understanding the genetic mechanism of the familial form of NPC was also discussed.     

Phase II study of the combination of carboplatin and 5-fluorouracil in metastatic nasopharyngeal carcinoma

 A carboplatin and 5-fluorouracil (CF) chemotherapy protocol was designed to evaluate tumor response and toxicity in patients with metastatic nasopharyngeal carcinoma (NPC). Patients with metastatic NPC were treated with a maximum of eight courses of CF. Carboplatin was given at 300 mg/m² by intravenous bolus on day 1 and 5-fluorouracil at 1 g/m² per day by continuous infusion on days 1 – 3; cycles were repeated once every 3 weeks. A total of 42 patients were evaluable for response and toxicity. They received a median of 6 courses (range 2 – 8) of chemotherapy. The overall response rate was 38% (16/42), comprising 7 complete responses (CR, 17%) and 9 partial responses (PR, 21%). The median survival was 12.1 months (range 6 – 54.2 months). The treatment was well tolerated. Toxicity was mainly bone marrow suppression. There were four episodes of neutropenic fever, but no renal toxicity or treatment-related death was documented. The combination of carboplatin given at a fixed dose of 300 mg/m² for 1 day and 5-fluorouracil given at 1 g/m² per day for 3 days produced an objective response rate of 38% and tolerable side effects. Received: 21 October 1995 / Recepted: 1 March 1996     

Chronic treatment with cisplatin induces replication-dependent sister chromatid recombination to confer cisplatin-resistant phenotype in nasopharyngeal carcinoma

Cisplatin can cause intrastrand and interstrand crosslinks between purine bases and is a chemotherapeutic drug widely used to treat cancer. However, the major barrier to the efficacy of the treatment is drug resistance. Homologous recombination (HR) plays a central role in restoring stalled forks caused by DNA lesions. Here, we report that chronic treatment with cisplatin induces HR to confer cisplatin resistance in nasopharyngeal carcinoma (NPC) cells. A high frequency of sister chromatid exchanges (SCE) occurs in the cisplatin-resistant NPC cells. In addition, several genes in the Fanconi anemia (FA) and template switching (TS) pathways show elevated expression. Significantly, depletion of HR gene BRCA1, TS gene UBC13, or FA gene FANCD2 suppresses SCE and causes cells to accumulate in the S phase, concomitantly with high γH2AX foci formation in the presence of low-dose cisplatin. Consistent with this result, depletion of several genes in the HR, TS, or FA pathway sensitizes the cisplatin-resistant NPC cells to cisplatin. Our results suggest that the enhanced HR, in coordination with the FA and TS pathways, underlies the cisplatin resistance. Targeting the HR, TS, or FA pathways could be a potential therapeutic strategy for treating cisplatin-resistant cancer.     

鼻咽癌放疗后颈动脉狭窄的临床分析

背景与目的:放射治疗是治疗头颈部恶性肿瘤主要手段之一.通过放疗以及放疗参与的多学科综合治疗能使约半数头颈部恶性肿瘤患者获得长期生存的机会.然而,放疗是否会造成颈部动脉血管的改变进而造成颈动脉狭窄,特别是鼻咽癌患者,放疗是否会造成此类损伤及损伤程度值得临床观察.本研究旨在探讨鼻咽癌放疗对颈动脉损伤的状况.方法:分析在复旦大学附属肿瘤医院接受放疗且生存达3年以上的鼻咽癌患者(研究组)与初治尚未接受放疗的鼻咽癌患者(对照组)的颈动脉狭窄状态,观察放疗后颈动脉损伤程度及影响其发生的临床因素.所有入组患者鼻咽部病理证实为低分化鳞癌.采用彩色多普勒超声检测患者双侧颈部血管情况,主要观察指标有血管内径、收缩期峰值流速及舒张末期血流速度.结果:研究组患者发生血管狭窄的情况比对照组更加明显和普遍,分别为80.0%和20.0%(P＜0.001),其中以颈总动脉及颈内动脉发生狭窄的情况更为常见[颈总动脉(70.0%:20.0%,P＜0.001):颈内动脉(63.3%:10.0%,P＜0.001);颈外动脉(30.0%:3.3%,P=0.015)].有意义的狭窄情况仅出现在研究组人群中(颈总动脉36.7%、颈内动脉23.3%、颈外动脉10.0%).结论:接受颈部放疗后生存3年以上的鼻咽癌患者,放疗后的颈动脉狭窄是常见临床现象.狭窄多见于颈总动脉和颈内动脉.     

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

Background: The most active chemotherapy regimens in UCNT were thosecombining anthracyclines (doxorubicin or epirubicin) and cisplatin. Ourprevious pilot study on 37 patients treated with thezorubicin–cisplatin combination with a RR of 67% and literaturedata about other anthracyclines such as epirubicin achieving a response rateof over 50% were the basis of this randomized study comparingefficacy and toxicity of the combination vs. zorubicin as monotherapy.Patients and methods: A total of 80 patients entered the study. Thediagnosis of UCNT was confirmed by two independent pathologists. Allpatients had their primary tumors in the nasopharynx. The patients wererandomized in two groups: group A (zorubicin 325 mg/m², day1), and group B (zorubicin 250 mg/m², day 1 and cisplatin 30mg/m², days 2–5). The inter-cycle interval was fourweeks. The two groups were well balanced according to sex, age, stage Ho andTNM stage.Results: Group A: 40 patients included, 34/40 evaluable for activity.Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intentto treat basis 8/40 (20%). Toxicity: granulocytopenia grade 3–46/40, thrombocytopenia grade 3–4 2/40, no febrile neutropenias,nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40other toxicities minor or absent. Group B: 40 patients included, 36/40evaluable for activity. Activity on evaluable patient basis: CR 10/36(27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36(75%); response rate on intent to treat basis 27/40 (67.5%).Toxicity: granulocytopenia grade 3–4 10/40, thrombocytopenia grade3–4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40,other toxicities mild or absent. Of the group of patients achieving a CR,four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up,one died after six months from fulminant hepatitis B and eight are incomplete remission lasting for 30+ to 66+ months. Following CR achievementnone received any consolidation radiotherapy, and the projected five yearsof freedom from relapse for complete responders is about 60%.Conclusion: Zorubicin is an effective drug in UCNT and its combinationwith cisplatin has a significant activity and an acceptable toxicity.     

Syncope as the initial presentation of nasopharyngeal carcinoma

Syncope can be the first manifestation of nasopharyngeal carcinoma (NPC). Recently, we have encountered one such case and was able to eradiate this symptom by combined chemotherapy and radiotherapy.