Comparative tolerability of chemotherapy regimens for germ cell cancer.

Germ cell tumours, even at an advanced stage, represent a unique model of malignant curable disease since >80% of patients are expected to be cured after appropriate therapy: surgery and radiotherapy in early stages, and chemotherapy and surgery in advanced stages. In advanced stages, serum tumour marker levels as well as extrapulmonary (brain, liver and bone) visceral metastases are the most important prognostic factors that affect treatment modalities. 'Gold standard' regimens for germ cell cancer currently include etoposide plus cisplatin with (BEP) or without (EP) bleomycin. In patients with good risk disease (90% cure rate), the optimal regimen of chemotherapy should combine the best efficacy and the least toxicity. As a result of randomised trials, 3 regimens can be currently recommended: (i) 4 cycles of EP; (ii) 4 cycles of BEP (with etoposide 350 mg/m2 per cycle); or (iii) 3 cycles of BEP (with etoposide 500 mg/m2 per cycle). In patients with poor risk disease, 4 cycles of BEP (with etoposide 500 mg/m2 per cycle) allow a disappointing cure rate of 50%. The long term toxicity of these regimens (gonadal toxicity and secondary malignancies) appears to be negligible and clearly does not challenge current standard strategies.     

Letrozole: a review of its use in postmenopausal women with breast cancer

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.     

Diagnosis and treatment of patients with testicular germ cell cancer.

Testicular germ cell tumours are a highly curable malignancy even in the presence of metastases, with an overall survival rate of approximately 90 to 95% when all stages are considered. Current therapeutic strategies aim at risk-adapted therapy, trying to maintain favourable overall results while reducing treatment-related toxicity, particularly in non-advanced disease. In stage I disease, unilateral inguinal orchiectomy represents the standard diagnostic and therapeutic approach. For patients with clinical stage I seminoma, prophylactic para-aortic radiotherapy with 26Gy is commonly employed. In patients with nonseminomatous germ cell tumours (NSGCT) at clinical stage I, the 3 options are: (i) retroperitoneal lymphadenectomy; (ii) a wait-and-see strategy; or (iii) 2 cycles of adjuvant chemotherapy. The individual risk profile for tumour recurrence, mainly based on histopathological criteria such as vascular tumour invasion, should guide treatment decisions in this group of patients. Radiotherapy is still the standard approach in clinical stage IIA/B seminoma, whereas in patients with a low tumour burden of NSGCT, retroperitoneal lymphadenectomy is frequently used followed by surveillance or adjuvant chemotherapy. Primary chemotherapy in these stages of disease may be at least equally successful. Major progress has also been achieved in the treatment of NSGCT patients with metastatic disease greater than clinical stage IIB, for whom primary chemotherapy represents the standard approach. After cisplatin-based combination chemotherapy, between 70 and 90% of patients will achieve a durable remission. In patients with 'good risk' metastatic disease, 3 cycles of cisplatin, etoposide and bleomycin (PEB) remain the standard treatment, despite several randomised trials trying to avoid the lung-toxic bleomycin or substituting cisplatin by carboplatin. In patients with 'intermediate' and 'poor prognosis' disease, 4 cycles of PEB given at 3-week intervals are considered routine treatment. The role of high dose chemotherapy with peripheral autologous blood stem cell transplantation is currently being investigated for patients presenting initially with advanced (poor prognosis) metastatic disease and for patients with relapse after previous chemotherapy, in whom conventional-dose salvage regimens will only result in 20% long-term survival. Because of the large group of patients with metastatic disease being cured, the possible long-term adverse effects of treatment have become important. Only a slightly elevated risk for therapy-related secondary malignancies has been identified. Long-term adverse effects associated with cisplatin may affect a larger proportion of patients. Further research should focus on reducing the risk of chemotherapy-related chronic toxicity.     

Oral etoposide in germ cell tumours

Patients with germ cell tumours who relapse or fail to achieve disease-free status after first-line chemotherapy have a poor prognosis. When administered orally, etoposide produces responses in approximately 25% of patients whose disease is refractory to therapy and is a reasonable choice for palliative treatment in patients who are otherwise incurable. Oral etoposide has also been studied as maintenance therapy in patients who have been treated with salvage chemotherapy or surgery, with results that compare favourably with historical data. We recommend 3 months of maintenance oral etoposide for patients who achieve a complete response to any type of salvage therapy.     

Description of patients with midgut carcinoid tumours: clinical database from a Danish centre

BACKGROUND: We have initiated a clinical database of patients with neuroendocrine tumours (n = 132). Data on patients with well-differentiated endocrine carcinoma (WHO classification) previous classified as midgut carcinoid patients, are presented. PATIENTS AND METHODS: Retrospectively, 56 patients with midgut carcinoid tumours were evaluated with respect to symptoms, primary tumour size, metastases, tumour markers, treatment and survival. RESULTS: Flushing was described in 29%, diarrhoea in 52%, abdominal pain in 34%, bronchial constriction in 2% and carcinoid heart disease in 4% of the patients. Fifty-two percent had liver metastases at referral. Twenty-seven percent were considered to have had radical surgery. Patients not considered for radical surgery and patients with liver metastases had significantly higher tumour marker levels (serum chromogranin A (CgA), serum serotonin and urinary 5-hydroxyindolic acid (5-HIAA)) compared to radically-operated patients and to patients without liver metastases (p<0.05, respectively). For all the midgut carcinoid tumour patients the overall 5-year survival rate was 72%. The radically-operated patients had a 5-year survival rate of 100% (other death causes excluded). The patients with normal CgA or <5 liver metastases at referral had a 100% 5-year survival rate. The patients with <5 liver metastases had a significantly better 5-year survival rate compared to patients with multiple liver metastases (100% vs. 50%, p<0.05). CONCLUSION: This group of patients exhibited the same characteristic clinical features with similar survival as reported from other specialised centres. Radical surgery, normal CgA level and <5 liver metastases indicated a good prognosis and patients with <5 liver metastases had a significantly better survival compared to patients with multiple liver metastases.     

调强放射治疗局部晚期鼻咽癌489例远期预后影响因素及晚期安全性研究

目的 探讨行调强放射治疗（IMRT）初治局部晚期鼻咽癌远期预后影响因素及晚期安全性。方法 回顾性纳入2012年1月至2017年12月于梅州市人民医院行IMRT一线治疗的局部晚期鼻咽癌病人共489例，分析随访生存情况、复发转移及晚期损伤情况，采用单因素和多因素评价局部区域控制率、总生存（OS）率及无复发生存（DFS）率独立影响因素。结果 489例病人随访5年局部区域控制率为92.64%(453/489),5年DFS率为84.05%(411/489),5年OS率为91.00%(445/489)。随访过程中死亡65例，其中因局部区域复发死亡25例，因远处转移死亡35例，因其他事件死亡5例。随访3～4级晚期损伤发生率为2.04%(10/489)；单因素分析结果显示，临床分期与IMRT一线治疗局部晚期鼻咽癌病人5年局部区域控制率有关（P<0.05）；性别、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年DFS率有关（P<0.05）；年龄、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年OS率有关（P<0.05）。Cox...     

The role of gemcitabine alone and in combination in the treatment of pancreatic cancer

Pancreatic cancer, one of the most frequently reported gastrointestinal tumors, has a 5-year survival of less than 5%. Despite representing only 2-3% of the total cancer incidence, it is the fifth leading cause of cancer death. This is because it is commonly only diagnosed at an advanced stage. Until recently the traditional therapy for patients with advanced disease was palliative 5-fluorouracil (5-FU)-based chemotherapy. However, the novel antinucleoside gemcitabine (Gemzar) has demonstrated a survival benefit over 5-FU, and an improvement in disease-related symptoms and quality of life in patients with advanced disease. This review presents an overview of the clinical studies of gemcitabine, either alone or in combination, with other chemotherapeutic agents and/or radiation therapy, in the treatment of these patients. A comparison of these studies is made with those using alternative treatment regimens. The data suggest that gemcitabine in combination with biomodulated 5-FU should be considered the standard palliative treatment to which other new drug combinations or combined modality chemoradiation regimens should be compared.     

卡培他滨间断用药治疗合并有多种慢性疾病的老年性晚期乳腺癌临床疗效分析

目的：观察卡培他滨间断用药治疗合并有多种慢性疾病的老年性乳腺癌患者的疗效及副作用。方法：26例晚期老年性乳腺癌患者,应用单药卡培他滨间断化疗。卡培他滨每日2500mg/m2,d1～14。中位化疗间隔时间为2.5个月,中位化疗周期为5个周期。结果：CR0例（0）,PR3例（11.6%）,SD18例（69.2%）,PD5例（19.2%）,1年存活率为92.3%,2年存活率为88.5%,3年存活率达76.9%。不良反应轻,主要为白细胞减少和胃肠道反应。对血糖、血压、心功能无明显影响。结论：对于合并有多种慢性疾病的老年性晚期乳腺癌,单药卡培他滨间断治疗是值得选择和进一步研究的治疗方案。     

肝切除术治疗原发性肝癌：附588例临床分析

对1959年9月～1993年4月行肝癌肝切除588例进行回顾，第一阶段（1959年9月～1985年12月）施行传统肝切除术142例，均为直径＞5cm中晚期肝癌，手术死亡率11％，术后3年和5年生存率分别为18％、7％。第二阶段（1986年1月～1993年4月）行肝癌肝切除术446例，以肝段切除及癌肿局部切除为主，采用多种技术改良及高新医疗设备，并予以化疗、免疫治疗等综合措施，手术死亡率＜2％，术后1年、3年、5年生存率分别为89％、55％、26％。     

Chemoradiotherapy for lung cancer

Chemoradiotherapy is a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of ～ 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is four cycles of chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation and prophylactic cranial irradiation after complete remission. A 5-year survival rate of ～ 25% is expected among patients treated for limited-stage small cell lung cancer. The incorporation of new agents, including target-based drugs, is one of the most promising strategies for improving the survival of patients.     

Chemoradiotherapy for lung cancer

Chemoradiotherapy is a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is four cycles of chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation and prophylactic cranial irradiation after complete remission. A 5-year survival rate of approximately 25% is expected among patients treated for limited-stage small cell lung cancer. The incorporation of new agents, including target-based drugs, is one of the most promising strategies for improving the survival of patients.     

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.     

76例腭部恶性肿瘤治疗临床分析

目的探讨腭部恶性肿瘤的治疗方法及其疗效。方法回顾性分析76例腭部恶性肿瘤经手术、放疗及手术和放疗联合治疗的临床疗效。结果鳞状上皮癌患者行单纯手术、单纯放疗、放疗联合手术治疗的5年生存率分别为40．0％、25．0％、57．9％。腺上皮癌患者行单纯手术、单纯放疗、放疗联合手术治疗的5年生存率分别为36．4％、30．0％、73．3％。结论腭部恶性肿瘤通过根治性手术治疗预后较好,手术配合放疗明显优于其他治疗方式。     

Phase II study of bendamustine in patients with relapsed or cisplatin-refractory germ cell cancer

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with incomplete response to first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. We investigated the efficacy and toxicity of bendamustine, a bifunctional alkylating benzimidol derivative with only partial cross-resistance to other alkylating agents such as ifosfamide or cyclophosphamide. Nineteen patients with cisplatin-refractory germ cell tumors (GCT) or relapse after high-dose chemotherapy plus autologous stem cell support were treated with bendamustine at a dose of 120 mg/m2 on 2 consecutive days at 3 week intervals. Patients had received a median of 9 (range 4-20) platinum-containing treatment cycles prior to bendamustine and 13 patients (68%) had previously received carboplatin/etoposide-based high-dose chemotherapy. One patient achieved a partial remission of only 6 weeks duration. No other responses were seen. Toxicity was low with one patient developing WHO grade 3 thrombocytopenia as the only WHO grade 3/4 toxicity observed. Hematologic toxicity was similar in patients pretreated with and without high-dose chemotherapy plus autologous stem cell support. We conclude that bendamustine has little or no clinically relevant activity in patients with cisplatin-refractory GCT or relapsed disease after high-dose chemotherapy.     

Pharmacotherapy for oesophagogastric cancer

Gastric cancer is the seventh and oesophageal cancer the ninth most common cancer in the UK, and >50% of patients present with locally advanced or metastatic disease. The incidence of oesophageal and oesophagogastric junctional tumours is increasing, making these important disease entities to understand and research. Despite improvements in surgical and peri-operative supportive care, 3-year overall survival with surgery alone for resectable disease is still poor. Outcomes in localised oesophageal cancer are improved with pre-operative chemotherapy, and in gastric cancer with peri-operative treatment or post-operative chemoradiotherapy. Oesophageal squamous cell carcinoma can be treated with definitive chemoradiotherapy as an alternative to surgery. While survival in patients presenting with metastatic disease is improved with the addition of systemic chemotherapy, median survival remains <1 year. Patients who are otherwise fit can be offered chemotherapy and this is superior to best supportive care. Regimens including a platinum and an anthracycline agent are favoured by the results of randomised trials. No standard second-line therapy has emerged. New research into taxanes has shown promising anti-cancer activity, and novel areas of investigation include incorporation of agents targeting vascular endothelial growth factor or epidermal growth factor receptor into standard regimens. This review focuses on the clinical trial evidence that dictates the optimal management of localised and advanced oesophagogastric cancer, focusing on pharmacotherapy. We examine areas of current research and highlight future therapeutic directions.     

利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤的疗效评价

目的 评价利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)的有效性及安全性.方法 回顾性分析甘肃省武威肿瘤医院血液科使用R-CHOP方案化疗后完全缓解的≥60岁的DLBCL患者86例,按其治疗方案分为2组.对照组患者在完全缓解后单用利妥昔单抗...     

Adjuvant therapy for pancreatic cancer

Ductal adenocarcinoma of the pancreas is one of the leading causes of cancer death in the UK, Europe and US, with incidence closely paralleling mortality. Until recently, enthusiasm for treating these patients was limited for a number of reasons: the majority of patients undergoing surgery would relapse early, adjuvant treatment was of unproven value and systemic therapy in advanced disease had only a small chance of a short-term benefit. More recently, however, it has become recognised that specialist surgery can improve results and there is evidence that adjuvant chemotherapy has a significant advantage in terms of 5-year survival. In particular adjuvant systemic 5-fluorouracil with folinic acid can result in 5-year survival of < or = 29% (compared with 11% for controls) and adjuvant gemcitabine can improve disease-free survival to 13.4 months from a median of 6.9 months in controls, but not overall survival. In contrast the role of adjuvant chemoradiation in addition to chemotherapy remains unproven and the survival results appear to be inferior to systemic chemotherapy alone. New agents, such as capecitabine and erlotinib, are emerging with some activity in this dismal disease signalling hope for the future.     

Randomized phase II trial of different schedules of administration of rebeccamycin analogue as second line therapy in non-small cell lung cancer

Summary Rebeccamcyin analogue (RA) is an antitumor antibiotic that results in DNA intercalation and topoisomerase I and II inhibition. Phase I trials of the daily × 5 schedule and once every 3 week schedule have been completed. Antitumor activity was observed during the phase I trials. The purpose of this study is to primarily determine the response rate of 2 different schedules of administration of RA in patients with advanced non-small cell lung cancer (NSCLC) who had progressed on one prior chemotherapy regimen. Secondary endpoints were median and 1-year survival rates. A two-stage Simon design was employed for both arms of the study. Patients were randomly assigned to either of two RA treatment schedules of 500 mg/m² as a 1 hr infusion repeated every 3 weeks (Arm A) or 140 mg/m²/day × 5 days repeated every 3 weeks (Arm B). Forty-two patients were randomized. No confirmed objective responses were seen. Stable disease was seen in 52% of patients on arm A and 37% on arm B. Median survival and 1 year survival rates were 5.6 months and 33.3% for arm A, 9.7 months and 42.1% for arm B respectively. Cox regression model demonstrated increased risk of death in patients younger than the age of 61 and for patients treated on arm A. RA failed to demonstrate a significant response rate in this disease setting, although the proportion of patients with stable disease and 1-year survival were encouraging and similar to other published studies of approved single agents for second-line therapy of NSCLC.     

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。