铂类药物治疗食管癌的临床研究进展

食管癌是我国最常见的恶性肿瘤之一,治疗采用手术、放疗、化疗综合治疗模式。食管癌化疗一直采用铂类药物为基础的联合方案。顺铂治疗食管癌疗效确切,用于新辅助化疗、辅助化疗,同期联合放疗和晚期病例的解救化疗。联合5-FU 的化疗方案在在食管癌同期放化疗、解救化疗中是被认为是标准方案。与顺铂相比,卡铂的肾毒性、胃肠道反应、耳毒性均低于顺铂,治疗食管癌并未显示出更多的优势。奥沙利铂治疗食管腺癌显示出较好的有效率和中位生存期,较顺铂降低了肾毒性和胃肠道反应,但外周神经毒性发生率高。奈达铂治疗食管鳞癌疗效确切,总体治疗效果不劣于含顺铂的联合方案,临床用于晚期食管癌的解救化疗、同期联合放疗等,因具较严重的骨髓抑制,代替DDP 用于食管鳞癌的一线治疗还需更加确凿的循证依据,对食管腺癌疗效尚不清楚。洛铂、5-FU 及亚叶酸钙联合方案治疗晚期食管癌疗效和安全性较好,主要不良反应是可逆性骨髓抑制和胃肠道反应,值得进一步研究。      

西妥昔单抗治疗头颈部鳞状细胞癌研究进展

常规放化疗治疗进展期头颈部鳞状细胞癌（HNSCC）的不良反应大，疗效有限。近期临床研究表明表皮生长因子受体（EGFR）抑制剂西妥昔单抗联合放疗治疗局部晚期HNSCC显示高效低毒的优越性，单药对铂类耐药病例仍有一定疗效。西妥昔单抗在HNSCC的综合治疗中有广阔的应用前景。     

奈达铂化疗同步放疗治疗局部晚期鼻咽癌45例

[目的]探讨奈达铂化疗同步放疗治疗局部晚期鼻咽癌的疗效和不良反应。[方法]84例局部晚期鼻咽癌患者,随机分为奈达铂组（45例）和顺铂组（39例）,两组在根治性放疗的同时给予奈达铂（奈达铂100mg/m^2静滴d1、22、43）或顺铂（顺铂100mg/m^2,静滴d1、22、43）化疗。[结果]奈达铂组CR42例（93.3%）,PR3例（6.7%）,顺铂组CR35例（89.7%）,PR4例（10.3%）,两组疗效差异无显著性（P〉0.05）。奈达铂组和顺铂组胃肠道反应发生率分别为22.2%和46.2%,差异有显著性（P〈0.05）,两组骨髓抑制、肝、肾功能损害、皮肤黏膜反应发生率差异均无统计学意义（P〉0.05）。[结论]奈达铂化疗同步放疗治疗局部晚期鼻咽癌疗效确切,不良反应可耐受。     

新辅助化疗对局部晚期宫颈癌手术疗效的影响

目的：探讨紫杉醇联合顺铂的新辅助化疗对局部晚期宫颈癌手术治疗疗效的影响。方法88例经病理证实的局部晚期宫颈癌患者随机分为2组,观察组44例接受紫杉醇联合顺铂的新辅助化疗＋宫颈癌根治术,而对照组44例仅行宫颈癌根治术。结果观察组44例局部晚期宫颈癌患者的手术时间为（200.5±56.3）min,术中出血量为（600.7±189.2）mL,术后宫旁淋巴结转移率为4.5％,术后盆腔淋巴结转移率为6.8％,均少于对照组44例局部晚期宫颈癌患者的（287.6±68.0）min、（850.5±200.7）mL、36.4％、40.9％,差异均有统计学意义（ P＜0.05）。化疗主要毒副反应为骨髓抑制、胃肠道反应、脱发、肌肉关节痛、周围神经毒性、肾功能损害等,经精心护理后化疗均得以顺利完成,未影响化疗的顺利进行。结论紫杉醇联合顺铂的新辅助化疗在局部晚期宫颈癌治疗中安全有效,有利于手术的顺利进行,并可减少复发转移风险,值得临床推广应用。     

奈达铂与顺铂单药周方案同步化疗治疗局部晚期鼻咽癌的疗效观察

目的：观察奈达铂（ NDP）和顺铂（ DDP）单药周方案同步化疗治疗初治局部鼻咽癌的毒副作用及近期疗效。方法初治局部晚期鼻咽癌患者60例,随机分成NDP组和DDP组,各30例。 NDP组化疗方案：0．9％氯化钠500 ml＋NDP 50 mg,静脉滴注,每周1次;DDP组化疗方案：0．9％氯化钠500 ml＋DDP 40 mg,静脉滴注,每周1次。2组均采用全程调强放疗。结果 NDP组和DDP组的呕吐发生率分别为53．3％、83．3％（P＜0．05）;血小板下降发生率分别为80．0％、50．0％（P＜0．05）;NDP组肾毒性发生率显著低于DDP组（P＜0．05）;2组白细胞下降、血红蛋白下降、肝脏毒性、口腔黏膜炎、耳神经毒性指标差异无统计学意义（P＞0．05）。2组有效率分别为93．4％、86．7％（P＞0．05）。结论NDP单药周方案同步化疗治疗局部晚期鼻咽癌的不良反应较DDP轻,患者依从性好,且与顺铂单药周方案同步化疗近期疗效相近。     

紫杉醇和顺铂联合放疗治疗老年晚期非小细胞肺癌疗效观察

目的研究紫杉醇和顺铂诱导化疗并同期联合放疗治疗不能手术的局部晚期非小细胞肺癌（NSCLC）的最佳治疗模式及疗效、预后和毒副反应。方法 82例局部晚期非小细胞肺癌患者,先给予紫杉醇和顺铂诱导化疗2周期,继之紫杉醇40 mg/m^2,静脉滴注,每周1次,并同期联合放疗,放疗结束后2月评价疗效。结果同步放疗、化疗的治疗总有效率为81.7%,1、2、3年生存率为78.6%、54.8%、38.1%,中位生存期19.6月,3年无进展生存率为26.8%（22/82）。治疗前后的QOL、KPS随机比较,差异有统计学意义（P〈0.01）。同步放疗、化疗期间入组患者其毒性可耐受,主要的急性毒副反应为白细胞下降、放射性肺炎和放射性食管炎;后期反应主要为肺纤维化和食管损伤,程度可接受,经对症处理均能耐受,均能顺利完成计划。结论每周紫杉醇联合同期放疗治疗局部晚期非小细胞肺癌有较好的疗效,值得临床应用。     

泰素联合卡铂化疗和同步放疗治疗局部晚期非小细胞的肺癌Ⅰ期？…

目的 评价泰素联合卡铂化疗和同步放疗在局部晚期非小细胞肺癌治疗中的疗效和毒性反应。方法 自１９９６年７月至１９９８年６月,１５例不能手术的初治局部晚期非小细胞肺癌患者行泰素联合卡铂化疗和同步放疗。ⅢＡ期７例（４７％）,ⅢＢ期８例（５３％）;鳞癌１４例（９３％）,腺癌１例（７％）。在放疗开始的第１天、第１５天和第２９天分别给予泰素４０ｍｇ／ｍ＾２（静滴１小时）和卡铂１５０ｍｇ／ｍ＾２,放疗总剂量为６     

精确放疗同步含顺铂方案化疗治疗局部晚期食管鳞癌的临床分析

目的 分析局部晚期食管鳞癌进行精确放疗同步顺铂或顺铂联合紫杉醇脂质体化疗的临床疗效及不良反应。方法 收集精确放疗同步含顺铂方案化疗的局部晚期食管鳞癌46例,其中单药顺铂化疗（RT+P组）26例,顺铂联合紫杉醇脂质体化疗（RT+TP组）20例。回顾性分析两种同步放化疗方法的近期疗效,1、2及3年生存率以及放射性食管炎、放射性肺炎、胃肠道反应、骨髓抑制等不良反应发生率,并与同期17例单纯放疗（RT组）病例进行比较。结果 三组患者观察期内均未出现Ⅳ~Ⅴ级不良反应。三组仅12%~15%的患者出现Ⅰ~Ⅱ级放射性肺炎,发生率低、程度轻,三组相互间差异无统计学意义（P=0.939）。RT组的Ⅰ~Ⅱ级胃肠道反应发生率及Ⅲ级骨髓抑制发生率均明显低于其他组。同步放化疗组的治疗有效率高于单纯放疗组,但差异无统计学意义（P=0.161）。同步放化疗组总的1、2、3年生存率及中位生存期均高于单纯放疗组。RT+TP组的生存率明显优于RT组（P=0.019）。结论 精确放疗同步顺铂联合紫杉醇脂质体化疗治疗局部晚期食管鳞癌,具有较好的近期疗效及生存获益,明显优于单纯放疗。     

奈达铂和5-FU联合放疗治疗晚期食管癌的疗效与毒性

外科技术和辅助治疗的进展已使晚期食管鳞癌的5年生存率提高到40％。在其治疗中已引入了术前化放疗，可缩小原发肿瘤，改善局部控制，防止远外转移。顺铂(CDDP)无论在联合化疗还是在化放疗中都是最有效和使用最广泛的药物。奈达铂是第2代铂类化合物，肾毒性较顺铂轻，髓系抑制和血     

三维适形放疗结合奥沙利铂为主的化疗治疗晚期直肠癌

目的 探讨三维适形放疗（3DCRT）结合奥沙利铂为主化疗治疗局部晚期和术后复发直肠癌的临床疗效。方法 66例局部晚期和术后复发直肠癌均在常规放疗44Gy后进入3DCRT，采用3DCRT结合奥沙利铂、氟尿嘧啶、亚叶酸钙同步化疗（综合组）34例，单独应用3DCRT（对照组）32例。综合组同步放化疗结束3～4周后，再巩固化疗2～3个周期。结果 综合组和对照组疼痛缓解率分别为97％和84％（P〉0．05）；有效率（CR＋PR）分别为91％和84％（P〉0．05）；2年局部控制率与局部无进展率之和分别为71％和66％（P〉0．05）；2年生存率分别为65％和38％（P〈0．01）；2年远处转移率分别为35％和63％（P〈0．01）。在毒副反应方面两个组相似（P〉0．05）。结论 三维适形放疗结合奥沙利铂为主化疗治疗局部晚期和术后复发直肠癌可明显减少远处转移率和提高2年生存率，且毒副反应可以耐受。     

Prospective pilot study of consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiotherapy for advanced head and neck cancer

PURPOSE: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. METHODS AND MATERIALS: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m(2), on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m(2), and cisplatin, 75 mg/m(2), every 3 weeks. RESULTS: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. CONCLUSION: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.     

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer

Purpose: To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. Materials and Methods: A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. Results: There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. Conclusions: The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.     

同步放化疗对宫颈鳞癌细胞增殖、凋亡及细胞周期的影响

目的:探讨局部晚期宫颈鳞癌细胞对同步放化疗应答的分子机制。方法:49例患者被分为2组:单纯放疗组(RT)和同步放化疗组(CCRT)。在治疗前和治疗中[RT组:放疗10 Gy后;CCRT组:放疗10 Gy+(DDP+5-FU)×1个周期]分别活检留取标本,用FCM、TUNEL及免疫组化检测细胞周期、凋亡以及PCNA的表达。结果:RT组和CCRT组治疗中较治疗前AI及凋亡阳性率均明显升高(P<0.05,P<0.001),治疗中CCRT组凋亡率显著高于RT组(P=0.03);PCNA的表达CCRT组较RT组降低更明显(P=0.005)。治疗中RT组细胞周期大部分被阻滞在G2/M期,而CCRT组大部分被同时阻滞在S和G2/M期。结论:CCRT治疗局部晚期宫颈鳞癌中化疗和放疗有协同作用,其机制可能为通过抑制细胞增殖以及阻滞细胞周期于S和G2/M期,使细胞周期同步化,继而诱导肿瘤细胞的凋亡实现的。     

Is trimodality approach better then bimodality in stage IIIA, N2 positive non-small cell lung cancer?

BACKGROUND: Neoadjuvant treatment followed by surgery is currently being investigated for locally advanced non-small cell lung cancer (NSCLC). This study reports efficacy, toxicity and feasibility of neoadjuvant chemotherapy with concurrent radiotherapy (CCRT) in stage IIIA, N2 positive NSCLC. METHODS: From March 2001 to February 2004, 52 patients with histologically confirmed stage IIIA, N2 positive NSCLC were registered. Patients received preoperative CCRT that consisted of weekly paclitaxel plus platinum chemotherapy and concurrent radiotherapy followed by surgery. RESULTS: Overall response rate was 76.9% (95% CI, 64-88%). The major grade 3-4 toxicities were radiation esophagitis (15.4%) and neutropenia (11.5%), and treatment-related mortality rate was 1.9%. Forty-two of 52 patients (80.8%) subsequently underwent surgical resection and 35 of 52 patients (67.3%) underwent complete resection. Among them, pathological complete response was obtained in 4.8%. Pathological downstaging rate to N0-1 and stage 0-II at surgery were 69.0% and 66.7%, respectively. The perioperative major morbidity rate was 23.8% and perioperative mortality was 2.4%. At a median follow-up of 33.9 months (range: 16.4-49.9), the median progression-free survival and overall survival were 16.5 months (95% CI, 6.2-26.8) and 25.6 months (95% CI, 14.6-36.6), respectively. Multivariate analyses identified that patients achieved mediastinal nodal clearance (downstage to pathological N0 or N1) after CCRT (p=0.02) and age at diagnosis<60 years (p=0.01) showed significantly improved survival. CONCLUSION: Neoadjuvant CCRT showed a high overall response rate with tolerable toxicity profile. Downstaging after CCRT may increase the rate of complete tumor resection and result in survival benefit in stage IIIA, N2 positive NSCLC patients.     

抗EGFR单抗类靶向药物在头颈部鳞癌综合治疗中的应用

头颈部肿瘤是世界上第6大常见的肿瘤。超过70%的头颈部肿瘤患者在首次确诊时即为局部晚期。尽管不断地努力改进治疗方法,但晚期病例的死亡率仍然居高不下。为了提高疗效,患者通常接受化疗、手术、放射治疗和分子靶向药物综合治疗。大量研究证实,表皮生长因子受体（epidermal growth factor receptor,EGFR）与肿瘤细胞的增殖和转移密切相关,EGFR在大多数头颈部肿瘤中高表达,对这些患者的预后有显著影响。抗EGFR单克隆抗体已经在一些国家被批准用于治疗局部晚期头颈鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）。本文综述了西妥昔单抗和尼妥珠单抗治疗HNSCC的研究进展。HNSCC的单克隆抗体靶向治疗,是选择西妥昔单抗还是尼妥珠单抗？本综述将围绕这一临床医生尤为关心的问题展开讨论。     

Chimioradiothérapie des cancers de l’œsophage : revue critique de la littérature

Locally advanced oesophageal cancer treatment requires a multidisciplinary approach with the combination of chemotherapy and radiotherapy for preoperative and definitive strategy. Preoperative chemoradiation improves the locoregional control and overall survival after surgery for locally advanced oesophageal cancer. Definitive chemoradiation can also be proposed for non-resectable tumours or medically inoperable patients. Besides, definitive chemoradiation is considered as an alternative option to surgery for locally advanced squamous cell carcinomas. Chemotherapy regimen associated to radiotherapy consists of a combination of platinum derived drugs (cisplatinum or oxaliplatin) and 5-fluorouracil or a weekly scheme combination of carboplatin and paclitaxel according to CROSS protocol in a neoadjuvant strategy. Radiation doses vary from 41.4 Gy to 45 Gy for a preoperative strategy or 50 to 50.4 Gy for a definitive treatment. The high risk of lymphatic spread due to anatomical features could justify the use of an elective nodal irradiation when the estimated risk of microscopic involvement is higher than 15% to 20%. An appropriate delineation of the gross tumour volume requires an exhaustive and up-to-date evaluation of the disease. Intensity-modulated radiation therapy represents a promising approach to spare organs-at-risk. This critical review of the literature underlines the roles of radiotherapy for locally advanced oesophageal cancers and describes doses, volumes of treatment, technical aspects and dose constraints to organs-at-risk.     

SEOM clinical guidelines for the treatment of head and neck cancer (HNC) 2013

Head and neck cancer represents 5 % of oncologic cases in adults. Early stage treatments are local with surgery and/or radiotherapy. For locally advanced stages, treatment requires radiotherapy combined with platinum-based drugs or cetuximab. Induction chemotherapy should be considered for selected cases. In the case of metastatic disease, adjuvant or palliative treatment is based on platinum agents and cetuximab.     

同步放化疗治疗局部晚期食管癌临床观察

目的 探讨同步放化疗治疗局部晚期食管癌的疗效及毒副反应.方法 80例经组织学或细胞学证实的局部晚期食管癌随机分为两组,同步放化疗组40例接受同步放化疗,单纯放疗组40例仅接受放疗,化疗采用DF方案,放疗剂量为60-64 Gy,治疗结束后分别观察疗效及毒副反应.结果 同步放化疗组和单纯放疗组有效率分别为95.0%、82....     

非手术方法治疗局部侵袭性胸腺肿瘤

背景与目的手术切除是早期胸腺肿瘤的主要治疗方法,而对于IV期的病变,化疗则是最常用的方案。对于局部晚期的肿瘤,尤其是不适合手术的病例,何种治疗方案效果更优则没有明确的结论。鉴于此,我们做了这项回顾性的研究,通过对三种非手术疗法的比较,希望找到一些线索。方法自2000年10月至2010年12月,共有42例患者接受了三种非手术方案的治疗。这三种模式分别是单独放疗（radiotherapy, RT）、序贯化放疗（se-quential chemoradiation, SCRT）以及同步放化疗（concurrent chemoradiation, CCRT）。并对三种方案的缓解率（objec-tive response rate, ORR）、总生存期（overall survival, OS）以及治疗的相关毒副反应进行比较。结果全组42例患者中,总的缓解率为61.9%,5年生存率为46%。RT组、SCRT组以及CCRT组的缓解率分别是43.8%、50%和87.5%（RT vs SCRT,P=0.692; RTvs CCRT,P=0.009; SCRTvs CCRT,P=0.051）。RT组、SCRT组以及CCRT组的5年生存率分别是30%、50%和61.9%（RTvs SCRT,P=0.230; RTvs CCRT,P=0.011; SCRTvs CCRT,P=0.282）。共有11例患者发生了3度-4度的中性粒细胞减少,其中7例出现在CCRT组,另4例出现在SCRT组。有9例患者主诉有3度放射性食道炎,其中RT组2例, SCRT组3例,CCRT组4例。另外,CCRT组还出现了2例3度的放射性肺炎。未发现致命的5度毒副反应。结论在治疗不适合手术的局部晚期胸腺肿瘤上,CCRT显示出了比RT和CCRT更好的局部控制以及长期生存优势,不过也有增加肺损伤风险的可能。对于局部侵袭性的胸腺肿瘤,CCRT可提供最佳的肿瘤控制效果。     

Recent advances in molecular-targeted drugs in head and neck cancer

Recently, the integration of radiotherapy and chemotherapy has advanced the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN), allowing functional organ preservation while improving locoregional control and overall survival compared with radiotherapy alone. However, as recurrences remain inevitable, there is an absolute need for alternative modes of therapeutic intervention. Moreover, the use of chemotherapy and radiotherapy also increases the incidence of toxicities such as mucositis, myelosuppression, xerostomia, and dysphasia. More recently, the use of molecular-targeted drugs, which minimally adds to the existing toxicities, along with cytotoxic drugs and radiotherapy has been intensively investigated. Cetuximab is a chimeric IgG1 monoclonal antibody that specifically blocks the epidermal growth factor receptor. In a randomized trial of radiotherapy with or without cetuximab for locally advanced SCCHN, the addition of cetuximab significantly improved the locoregional control and overall survival without an increase in adverse events. Furthermore, a randomized trial of 5-FU and cisplatin with or without cetuximab for recurrent/metastatic SCCHN demonstrated a significant survival benefit for cetuximab combination arms compared with 5-FU and cisplatin arms alone. Based on these findings, many molecular-targeted drugs have been investigated in the treatment of the head and neck cancer to ensure better clinical outcomes in the near future.