Current chemotherapy options for thymic epithelial neoplasms

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.     

Influence of the adjuvant therapy on the survival of patients with stage II pancreatic carcinoma

This study aimed to investigate the effect of adjuvant therapy on the treatment of stage II pancreatic carcinomas. The clinical data of 139 cases of stage II pancreatic carcinoma were analyzed retrospectively. The overall 1-, 3-, and 5-year cumulative survival rates of 139 patients were 40%, 6%, and 3%, respectively, and the median survival time (MST) was 279 days. The MST was 399 days for those with adjuvant therapy, 210 days for those without adjuvant therapy, 390 days for the radical resection group, 270 days for the bypass operation and laparotomy group, and 132 days for the nonsurgical group. The adjuvant therapy could not prolong the survival time and decrease the liver metastasis rate of the patients with stage II carcinoma significantly in radical resection group (P>0.05). In the bypass operation and laparotomy group and nonsurgical group, the adjuvant therapy could improve the survival of the patients significantly (P<0.05); however, the survival rate was not significantly different among systemic venous chemotherapy, radiation therapy, interventional therapy, and combination therapy (P>0.05); or between gemcitabine (GEM) regimen and 5-fluorouracil regimen (P>0.05); or between GEM monotherapy and GEM combined with platinum/capecitabine (P>0.05). The proper adjuvant therapy can be suggested according to the general condition of the patients after radical resection for stage II pancreatic carcinoma. Chemotherapy combined with radiation should be applied actively for the patients whose cancerous tissues were not radically resected. The clinical efficacy of GEM combined with platinum/capecitabine is relatively better than GEM.     

Neoadjuvant chemotherapy in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those patients who present with stage I-IIIA disease and are resected will experience distant relapse. Postoperative adjuvant chemotherapy has been evaluated in several randomized trials but the results of these trials have been inconclusive with increased survival reported in few trials. In resectable stage IIIA NSCLC the findings of three randomized trials have indicated that the survival of these patients is better with neoadjuvant chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been carried out with encouraging results. The majority of patients with stage IIIA NSCLC require multimodality therapy if they are to achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC continues to evolve and is a subject of ongoing research. One focus for present research is to integrate new active agents into the neoadjuvant setting. Another challenge is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible, does not appear to compromise surgery and yields high response rates. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse.     

新辅助放化疗对中晚期食管癌患者疗效的护理观察

目的：观察中晚期食管癌患者外科手术前新辅助放化疗的临床护理疗效。方法：试验组136例患者在放疗基础上术前采用2个周期的顺铂加氟尿嘧啶的化疗方案,化疗后2周手术;对照组136例患者无化疗行直接手术。结果：试验组肿瘤明显缩小,其中根治性切除112例,占82.35％;对照组根治性切除89例,占65.44％。两组对比差异显著（P<0.01）。结论：术前新辅助放化疗可降低食管癌肿瘤分期,提高根治性切除手术率,提高术后生存率及生存质量。     

Lung cancer: a review.

The frequency, risk factors, pathophysiology, diagnosis, and management of lung cancer are reviewed. An estimated 157,400 Americans died of lung cancer in 2001. Lung cancer is the second most frequent cancer in both men and women. The major risk factor for lung cancer is smoking, which accounts for 75-80% of lung cancer-related deaths. Lung cancers can be broadly classified into two forms, small-cell carcinomas and non-small-cell carcinomas. Non-small-cell lung cancer is more common, accounting for up to 75% of lung cancers. Lung cancer is diagnosed by chest radiography, sputum cytology, bronchoscopy, needle biopsy, and other techniques. Surgery plays a major role in managing stage I and stage II non-small-cell lung cancer and may be used for stage III disease. Patients with stage IIIa disease may be surgical candidates, but involvement of mediastinal lymph nodes reduces the probability of survival. Adjuvant irradiation may reduce the rate of local recurrence but does not increase survival time. Adjuvant chemotherapy may confer a small survival-time advantage if the regimen includes cisplatin. Chemotherapy combined with radiation therapy may produce a survival advantage over irradiation alone. Patients with advanced non-small-cell lung cancer should receive combination chemotherapy. Several regimens have shown a survival advantage over best supportive care. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan have activity both as single agents and in combination. Surgery has only a limited role in the management of small-cell lung cancer. Patients with limited disease should receive a platinum-based chemotherapy regimen plus radiation therapy. Combination chemotherapy should be offered to patients with extensive disease. The most active regimens contain cisplatin or carboplatin. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan combinations have shown some promise. Lung cancer, although highly preventable, is usually diagnosed at an incurable stage. Chemotherapy is playing an increasingly important role alongside surgery and radiation therapy in the management of this disease.     

Novel strategies for systemic treatment of endometrial cancer

The median survival of women with advanced or recurrent endometrial cancer is less than one year. Of the women with early stage endometrial cancer and poor prognostic factors like high grade or deep myometrial invasion, 40% will recur. Over the last decade, incredible strides have been taken in evaluating systemic therapy for this disease, however, survival rates remain poor. Progestin therapy offers a 10 - 20% response rate and survival of less than one year. Progestins are most effective in women with well-differentiated tumours and long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with most activity include ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40 - 60%, however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e., LY-353381.HCl and letrozole), chemotherapeutics (i.e., paclitaxel), evaluating chemotherapeutic agents in combination (i.e., paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma (i.e., Herceptintrade mark). Exciting developments in the understanding of the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.     

Novel strategies for systemic treatment of endometrial cancer

The median survival of women with advanced or recurrent endometrial cancer is less than one year. Of the women with early stage endometrial cancer and poor prognostic factors like high grade or deep myometrial invasion, 40% will recur. Over the last decade, incredible strides have been taken in evaluating systemic therapy for this disease, however, survival rates remain poor. Progestin therapy offers a 10 - 20% response rate and survival of less than one year. Progestins are most effective in women with well-differentiated tumours and long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with most activity include ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40 - 60%, however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e., LY-353381.HCl and letrozole), chemotherapeutics (i.e., paclitaxel), evaluating chemotherapeutic agents in combination (i.e., paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma (i.e., Herceptin?). Exciting developments in the understanding of the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.     

声门上型喉癌术前辅助化疗的临床探讨

摘要 目的 探讨术前辅助化疗在声门上型喉癌的治疗中对手术切除率 、淋巴结转移率、患者生存质量和预后的影响。方法 对1995年5月～2005年12月收治的104例声门上型喉癌行回顾性分析,按2002AJCC分期：临床Ⅰ期7例,Ⅱ期30例,Ⅲ41例,Ⅳ26例, 63例术前予化疗（Ⅰ期5例,Ⅱ期18例,Ⅲ24例,Ⅳ16例）。化疗前后行纤维喉镜及CT检查,化疗后一周行手术。生存分析采用Kaplan-Meier法,各因素间比较用Log-rank检验,多因素分析采用Cox模型。结果：行术前化疗的患者,经喉镜、CT、术中评估及术后病理证实,完全化解者（CR）7.93％(5／63),部分缓解者（PR）44.44％(28／63),总有效率(CR+PR) 52.37％,用Log-rank法比较术前化疗组与非化疗组生存期,术前辅助化疗对远期生存有统计学意义(P =0.03),多因素Cox模型分析表明：N分期,pTNM组织病理学分级与复发是影响生存的独立危险因素（P 均<0.05）。术前诱导化疗是生存的保护性因素（P <0.05）。结论：声门上型喉癌的预后与T分期、N分期、pTNM组织病理学分级、术前化疗及复发等多因素相关。术前辅助化疗,可以提高患者生存率,提高手术切除率,改善预后。     

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.     

Chemoradiotherapy: the new standard care for invasive cervical cancer

Cervical cancer remains a major health problem worldwide, despite advances in screening. For patients with locally advanced stage disease, failure to obtain local-regional control usually results in death. In an effort to improve local-regional tumour control, neoadjuvant and concurrent chemoradiation have been tested. Recently, 5 randomised trials performed by the Gynecologic Oncology Group, Radiation Therapy Oncology Group and the Southwest Oncology Group studying cisplatin-based chemoradiation have demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and 2 trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all trials, cisplatin-based chemotherapy administered concurrently with radiation therapy was the more effective therapy, reducing the risk of death by 30 to 50%. Acute toxicities, principally neutropenia and gastrointestinal, were more common with chemoradiation but were transient and rates of late complications were similar between treatment groups. Based on the results of these 5 randomised trials, the National Cancer Institute released a Clinical Announcement stating that cisplatin-based chemotherapy as used in these trials concurrently with radiation therapy should be the new standard of therapy for high risk early stage and locally advanced stage cervical cancer.     

Optimal therapeutic strategies for resectable oesophageal or oesophagogastric junction cancer

Oesophageal cancer is the eighth most common cancer diagnosed worldwide, with almost half a million new cases diagnosed each year. Despite improvements in surgical and radiotherapy techniques and refinements of chemotherapeutic regimens, long-term survival, even from localized oesophageal cancer, remains poor. Surgical resection alone remains the standard approach for very early stage disease (stage I), but whilst surgery remains fundamental to the treatment of stage II-III resectable adenocarcinoma, multimodality therapy with chemotherapy or chemoradiation (CRT) is internationally accepted as the standard of care. Data from two large, randomized phase III trials support the use of perioperative combination chemotherapy in lower oesophageal and oesophagogastric junction adenocarcinomas, but the contribution of the adjuvant therapy is uncertain. There are conflicting data from randomized studies of a purely neoadjuvant approach; however, recent meta-analyses have demonstrated that chemotherapy or CRT given prior to radical surgery improves survival in patients with adenocarcinoma of the oesophagus. Neoadjuvant CRT but not chemotherapy alone is also beneficial for patients with squamous cell carcinoma. Definitive CRT has emerged as a useful option for the treatment of resectable squamous cell carcinoma of the oesophagus, avoiding potential surgical morbidity and mortality for most patients, with salvage surgery reserved for those with persistent disease. In this review, we focus on the pharmacotherapy of resectable oesophageal and oesophagogastric junction cancers and how clinical trials and meta-analyses inform current clinical practice.     

紫杉醇联合卡铂在宫颈癌新辅助化疗中的50例临床分析

目的探讨紫杉醇联合卡铂(TC方案)在宫颈癌新辅助化疗中的临床疗效。方法选取2003年1月至2007年6月在郑州大学第二附属医院经病理确诊的50例宫颈癌患者,回顾分析其临床资料。结果 TC方案新辅助化疗的临床有效率为94%,临床完全缓解的患者6例,占12%,部分缓解的患者41例,占82%,临床稳定的患者3例,占6%,无进展病例;47例化疗后行广泛子宫切除加盆腔淋巴结清扫术,术后病理报告切缘均未见癌转移;6例术后病理报告宫颈局部未见浸润癌,其中3例经多处取材未见癌残留,3例变为原位癌;淋巴结转移的患者有12例,占24%,术后追加放射治疗;所有患者随访至2008年6月底,除3例因期别较晚,化疗效果不满意转外院行放射治疗失访外,未见复发病例。结论宫颈癌TC方案的术前全身新辅助化疗操作方法简便,可提高其近期疗效,值得推广应用。     

Lung microcytoma: a multidisciplinary therapeutic approach.

This report is of 26 patients diagnosed with microcytoma of the lung in stages I, II, and IIIa. All patients received surgical treatment as well as postoperative chemoradiotherapy when indicated by stage. Mean survival rates were 16 months for stage 1, 10 months for stage II and 6 months for stage IIIa disease. For many years surgery was considered contraindicated in the treatment of pulmonary microcytoma. Now a multidisciplinary approach is being used in which surgery has a crucial role. Microcytoma of the lung has a poor prognosis due to its early metastasis and rapid growth. It is crucial to have early diagnosis and accurate, consistent staging as the basis for treatment. A review of literature shows that the use of surgery, chemotherapy and radiotherapy are all important in treatment of microcytoma. Chemotherapy is successfully utilized preoperatively to improve local control, decrease neoplastic mass, induce histological regression and as postoperative adjuvant therapy. Radiotherapy has been shown to be effective preoperatively to reduce local mass and prophylactically for cerebral metastasis. Surgery is crucial to irradicate the neoplastic mass, improve staging accuracy, decrease the possible selection of neoplastic clones resistant to postoperative therapy, decrease local recurrence and allow less aggressive chemoradiotherapy. We feel the most effective protocol for pulmonary microcytoma includes preoperative chemotherapy and radiotherapy when indicated followed by surgical intervention and finally successive adjuvant therapy. The limited number of our cases does not consent a statistically significative conclusion. Our data confirm the importance of the surgical procedure in stages I and II, where according also to other authors, the best results are obtained. Surgical indication in stage IIIa is still discussed due to precocius lymphnode dissemination that significantly affects long-term survival.     

Therapeutic strategies in neoadjuvant therapy of non-small cell lung cancer: benefits of gemcitabine

Stages of non-small cell lung cancer (NSCLC) that are potential candidates for surgical resection have been treated in several ways: surgery alone is curative in only two-thirds of cases and post-operative radiotherapy (RT) provides only weak control of advanced-stage disease. Since metastatic recurrence is due to the presence of micrometastases, chemotherapy (CT) can be envisaged, even at an early stage of the disease--first with the CT/RT induction combination, which improves survival (median survival: 15 months) and the resection rate (70%). Recent studies on neoadjuvant therapy have evaluated the usefulness of different induction CT regimens. Among these, the gemcitabine/cisplatin study protocol (GC), set up in a phase II study for patients with stage IIIA N2 NSCLC, was very effective [objective response (OR): 70.2%; median survival: 19 months] and should be promising for stages IB and II. Other studies involving platinum analogs have shown good OR rates inducing a high resection rate and a reduction in the spread to mediastinal lymph nodes. Major studies are ongoing, one of which compares GC + surgery versus surgery alone (stages IB-IIIA); the other regimen aims to evaluate GC versus paclitaxel/carboplatin as well as two induction strategies.     

100例乳腺癌保乳综合治疗临床分析

目的 研究乳腺癌保乳综合治疗的方法与疗效。方法 100例Ⅰ～Ⅱ期原发性乳腺癌病例施保乳手术（局部乳腺切除＋腋淋巴结清扫术）、术中或术后瘤床插植近距放疗＋化疗。手术后2～4周再接受全乳腺外照射剂量为50Gy。激素受体阳性的患者均接受三苯氧胺治疗,随访时间中位数为42个月。结果 经随访10～96个月,平均42个月,双乳对称,外形美观。无1例出现局部复发,无死亡病例,1例出现骨转移。结论 Ⅰ～Ⅱ期乳腺癌实施保乳综合治疗,可以取得满意的临床效果,可成为早期乳腺癌的首选治疗方法。     

男性乳腺癌6例临床分析

目的：探讨男性乳腺癌的特点及影响预后的因素。方法：总结6例男性乳腺癌患者,对其发病特点及诊治情况进行分析,治疗均采用手术切除加术后化疗、放疗及内分泌治疗。结果：6例患者中5年生存率为43%。结论：男性乳腺癌发病率低,发病病程长,病理类型以浸润性导管癌为主,临床分期较晚,癌组织细胞分化较低,预后较差,易早期转移。治疗上应以根治术为主、放疗化疗为辅的综合治疗。     

以手术为主的综合治疗对食管小细胞癌患者生存期的影响

目的 对我院确诊的17例原发性食管小细胞癌( PESC)的临床特点、治疗方法和预后进行总结,分析以手术为主的综合治疗方法对患者生存期的影响.方法 17例PESC中单纯食管癌根治术2例,单纯放射治疗(放疗)3例,手术+放化疗4例,放疗+化疗7例,单纯化疗1例.化疗采用EP、FP方案,即依托泊苷加顺铂注射液、氟尿嘧啶加顺铂注射液,手术+放化疗者手术后化疗1～2个周期再放疗后再化疗2～3个周期,放疗+化疗者放疗后再化疗3～6个周期.结果 1例广泛期患者单纯化疗后5个月内死亡,5例局限期患者行单纯局部治疗(单纯手术或单纯放疗),1年生存率40.0％(2/5),2年生存率0％.11例局限期患者接受综合治疗(手术+化疗+放疗或化疗+放疗),1年生存率为63.6％( 7/11),2年生存率为54.5％ (6/11),3年生存率为18.1％ (2/11),中位生存期为14个月.综合治疗较单纯治疗生存期有所延长.结论 对PESC患者采用以手术为主的综合治疗方法,有可能延长患者的生存期.     

Induction chemotherapy in head and neck cancer: a new paradigm

Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a high cure rate while preserving functions. Treatment strategies are designed according to the disease stage, primary site, operable status, patient age, and performance status. Surgery, radiation therapy, chemotherapy, and more recently molecular-targeted therapies are part of these strategies, but their sequence remains to be defined. Over the last 30 years, induction chemotherapy has attained an important position in the management of patients with locally advanced squamous cell carcinoma, particularly since the introduction of taxanes. The decision to deliver induction chemotherapy (and its intensification) must be considered in the light of other treatments aiming at better locoregional control (normofractioned radiotherapy, accelerated or hyperfractionated radiotherapy, addition of concurrent chemotherapy, or of targeted therapy) with or without adjuvant treatment. This review summarizes the rationale, these data, and perspectives on induction chemotherapy-based strategies.     

老年胃癌患者468例临床病理及预后分析

目的探讨老年胃癌的临床病理特点及影响预后的相关因素。方法对我院近10年收治的468例老年胃癌患者的临床病理、治疗及其与预后的关系进行分析。结果老年人胃癌组织学以低分化腺癌和黏液腺癌为主;病变部位以胃窦部及胃体部为主;临床分期以Ⅲ、Ⅳ期多见;治疗以手术治疗为主。病变部位、临床分期、根治性手术切除是影响预后的主要因素。结论早期诊断、及时治疗及行根治性手术切除,是改善老年胃癌患者预后的关键。     

Management of bile duct tumors

Cholangiocarcinomas are a rare but highly fatal disease. The only curative treatment is radical surgical resection of the tumor and the regional lymph nodes. More than half of patients have irresectable disease, which implicates a median survival of < 1 year. The mainstay of palliative treatment is endoscopic or percutaneous drainage of the biliary system. In patients with good performance status, palliative chemotherapy seems to provide some survival benefit together with an improved quality of life. No standard chemotherapy has been defined but gemcitabine monotherapy or the combination of gemcitabine with platin derivates or capecitabine seems to be more effective than other protocols. Additionally, photodynamic therapy has shown promising results and radiation might be helpful for localized disease. In a very selected population liver transplantation can also be an option.