Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial

A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy (methotrexate and doxorubicin) or symptomatic treatment only. In the whole study 196 (32.1%) had limited disease and 414 (67.9%) extensive disease. During initial chemotherapy the response rate (complete and partial responses) after four courses of treatment was 61% with no significant increase in patients receiving eight courses (63%). In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy (25.6%) over those receiving eight (18.7%). The overall results show that of the four possible treatment randomizations, four courses of chemotherapy alone is inferior in terms of overall survival (30 weeks median survival) to the other three treatment options (39 weeks median survival, P less than 0.01). In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent (median survival of 40 weeks versus 49 weeks, P = 0.003) but not if drug treatment was given on relapse. The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival, but this is not the case if chemotherapy is given at relapse.     

局部晚期非小细胞肺癌治疗策略的新进展

对局部晚期肺癌的治疗不仅要考虑到局部,更要兼顾到全身,任何一种单一治疗(如单手术、化疗、放疗)均不可能有效地提高患者的长期生存率,只有采用多学科治疗,才有可能取得较好的治疗效果。本文就近年,尤以2007年以来最新的肺癌多学科治疗治疗策略作以综述。     

Treatment of lung cancer--state of the art in 2000

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.     

Effective evaluation of combination chemotherapy in stage I-II of non-Hodgkin's lymphoma--a comparison of treatment with multivariate analysis

Sixty-one patients with non-Hodgkin's lymphoma (Stage I and II) were treated solely with radiotherapy or in combination with chemotherapy. A multivariate analysis was used to identify the prognostic factors that significantly affected the treatment outcome. The variables examined included: stage of disease, according to the Ann Arbor classification, sex, age, pathological criteria, according to the LSG, the presence or absence of systemic symptoms, the sites of disease involvement, the LDH, the bulk of the disease, and the combination chemotherapy. Variables achieving a p-value in the 0 to 0.10 range with a multivariate analysis for the overall survival were the stage of disease, the sites of the disease involvement, the bulk of the disease, and the combination chemotherapy. Finally, the overall survival was affected by bulk of the disease (p less than 0.01) and the combination chemotherapy (p less than 0.01). The 5-year survival rates were 84.4% for stage I and 50.7% for stage II. The survival rates were 47.5% for radiotherapy treatment alone and 75.3% for combination chemotherapy. It thus was concluded that combination chemotherapy was effective for treatment of stages I and II of non-Hodgkin's lymphoma.     

Extending the duration of first-line chemotherapy in metastatic breast cancer: a perspective review

The treatment of metastatic breast cancer is mainly palliative, but optimal management might result in survival improvement as well. For this reason, many trials have attempted to optimize the therapeutic approach in this disease setting. Among the possible options, chemotherapy represents the backbone of the treatment and survival improvements that have been shown by the use of modern chemotherapeutic agents. Whereas the type of chemotherapy is generally dictated by patient characteristics and those of their disease, substantial controversy still remains on how long chemotherapy should be administered after disease control is achieved. In this review, we have analysed all available evidence on the duration of first-line chemotherapy in advanced breast cancer.     

Adjuvant Chemotherapy and Prognostic Factors in Stage II Colon Cancer - Izmir Oncology Group Study

Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefitis not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patientswith low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancerpatients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patientswho were diagnosed with stage II colon cancer between January 2006 and December 2011 were included inthe study. Patients were stratified into two groups as being low-risk and high-risk according to risk factorsfor stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with riskfactors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival andoverall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysisdemonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowelperforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions:The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was foundthat adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact thatprognosis of stage II patients is good, many more patients will be needed for statistically significant differences insurvival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients althoughit is not a standard treatment approach.     

Multi-drug Combination Therapy with Vincristine-Melphalan-Cyclophosphamide-Prednisolone Was More Effective than Cyclophosphamide-Prednisolone in Stage III Myeloma

A cooperative randomized clinical trial to compare the effectiveness of multi-drug combination chemotherapy (VMCP, vincristine-melphalan-cyclophosphamide-prednisolone) with CP (cyclophosphamide-prednisolone) for the treatment of multiple myeloma was performed. When the whole group of patients was evaluated, the choice of chemotherapy (VMCP or CP) was not a significant prognostic factor associated with response or survival by uni- or multivariate analysis, and the difference between the survival curves of the treatment groups was only marginally significant. However, when the analysis was confined to stage III patients, the choice of chemotherapy became a significant prognostic factor associated with both response rate and survival, and the statistical difference between survival curves was significant. Taking the disease characteristics of multiple myeloma into consideration, the better result obtained with multi-drug combination chemotherapy in the treatment of stage III patients is consistent with other studies supporting the superiority of multi-drug combination chemotherapy for patients with overt systemic disease.     

Multi-drug combination therapy with vincristine-melphalan-cyclophosphamide-prednisolone was more effective than cyclophosphamide-prednisolone in stage III myeloma. The Nagoya Myeloma Cooperative Study Group

A cooperative randomized clinical trial to compare the effectiveness of multi-drug combination chemotherapy (VMCP), vincristine-melphalan-cyclophosphamide-prednisolone) with CP (cyclophosphamide-prednisolone) for the treatment of multiple myeloma was performed. When the whole group of patients was evaluated, the choice of chemotherapy (VMCP or CP) was not a significant prognostic factor associated with response or survival by uni- or multivariate analysis, and the difference between the survival curves of the treatment groups was only marginally significant. However, when the analysis was confined to stage III patients, the choice of chemotherapy became a significant prognostic factor associated with both response rate and survival, and the statistical difference between survival curves was significant. Taking the disease characteristics of multiple myeloma into consideration, the better result obtained with multi-drug combination chemotherapy in the treatment of stage III patients is consistent with other studies supporting the superiority of multi-drug combination chemotherapy for patients with overt systemic disease.     

Chemotherapy in the management of squamous-cell carcinoma of the head and neck

Previously reserved for palliation, chemotherapy is now also a central component of several curative approaches to the management of patients with advanced-stage head and neck cancer. Here we review the results of both induction chemotherapy and chemoradiotherapy trials in patients with curable disease, and chemotherapy trials in patients with recurrent and metastatic disease, and we highlight current areas of investigation. Compared with traditional treatment modalities, chemotherapy given on induction schedules to patients with advanced laryngeal cancer allows greater organ preservation without compromise to survival; when given concomitantly with radiotherapy to patients with resectable or unresectable advanced disease, chemotherapy again improves survival.     

Chemotherapy for metastatic breast cancer

The treatment of metastatic breast cancer aims to relieve symptoms by controlling disease and prolonging survival with better QOL. The meta-analysis demonstrated the significant advantage for overall survival by chemotherapy with a longer period. It means that chemotherapy can prolong survival. The major chemotherapies contain anthracyclines or taxanes. For HER 2-overexpressing breast cancer, a standard treatment utilizes trastuzumab-containing chemotherapy. The other active agents include vinorelbine, capecitabine, S-1, mitomycin and gemcitabine. Bisphosphonates combined with chemotherapy or hormone therapy are able to alleviate pain or complications of osteolytic bone metastasis. Experimental agents, such as monoclonal antibody or small molecular kinase inhibitor, are investigated for clinical use. The treatments, either chemotherapy or hormone therapy, could be performed in sequence in order to minimize toxicities and maximize efficacy. In selecting the most appropriate treatment for metastatic breast cancer, it is recommended to consider patients' preference by providing the correct information on the status of disease, efficacy and toxicities of chemotherapy.     

Induction chemotherapy for resectable non-small-cell lung cancer

Lung cancer remains the leading cause of cancer death in American men and women. Non-small-cell lung cancer (NSCLC) accounts for 85% of these cases. Although surgery is the best curative approach for resectable NSCLC, long-term survival for patients with operable disease remains poor. More than half of patients who initially present with stage I to IIIA disease experience relapse of metastatic disease. Postoperative adjuvant therapy has been evaluated in several randomized trials, and provides a survival benefit. It appears reasonable to look to induction chemotherapy, or preoperative chemotherapy, to provide a similar improvement in survival with early treatment of micrometastatic disease. Multiple trials of induction therapy have been carried out with encouraging results. The use of various induction regimens with chemotherapy alone or chemotherapy combined with radiotherapy for stage IIIA NSCLC is under investigation. Randomized trials are under way to better define the role of induction therapy in the multimodality treatment of NSCLC.     

Curative strategies for liver metastases from colorectal cancer: a review

Colorectal cancer is a very common malignancy and frequently manifests with liver metastases, often without other systemic disease. Margin-negative (R0) resection of limited metastatic disease, in conjunction with systemic antineoplastic agents, is the primary treatment strategy, leading to long survival times for appropriately selected patients. There is debate over whether the primary tumor and secondaries should be removed at the same time or in a staged manner. Chemotherapy is effective in converting some unresectable liver metastases into resectable disease, with a correspondingly better survival outcome. However, the ideal chemotherapy with or without biological agents and when it should be administered in the course of treatment are uncertain. The role of neoadjuvant chemotherapy in initially resectable liver metastases is controversial. Local delivery of chemotherapy, with and without surgery, can lead to longer disease-free survival times, but it is not routinely used with curative intent. This review focuses on methods to maximize the disease-free survival interval using chemotherapy, surgery, and local methods.     

Thyroid lymphomas stages IE and IIE: comparative results for radiotherapy only, combination chemotherapy only, and multimodality treatment

This study was undertaken to ascertain the influence of both more precise staging and more intensive treatment on results in 38 patients with Stage IE and IIE lymphomas of the thyroid. These patients were admitted between 1947 and 1984. Using the modified Rappaport system, the disease was classified as diffuse large cell in 32 patients. The initial investigation included lymphangiography in 25 patients, five of which had a staging laparotomy. The assigned stages were IEA--11, IEB--1, and IIEA--26. Treatment consisted of definitive radiotherapy alone in 15; combination chemotherapy and radiotherapy in 14; and chemotherapy alone in 6 patients. The remaining three patients were treated with surgery alone. In general, combination chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, and prednisone, with or without bleomycin (CHOP +/- Bleo). The overall 5-year survival and disease-free survival were 72 and 64%, respectively. For patients treated with radiotherapy only, results depended on stage. For Stage IE, the survival and disease-free survival were 100 and 83%, respectively. The corresponding Stage IIE results were 88 and 75%. Within this group, results were better for a subset of patients where disease did not involve the mediastinum. Survival and disease-free survival for combined modality treatment were both 77% (10 of these 17 patients had Stage IIE disease). Survival and disease-free survival for combination chemotherapy were 53 and 30% (all had Stage IIE disease). In conclusion, radiotherapy alone is excellent treatment for disease limited to the thyroid with or without cervical adenopathy. Results for patients with mediastinal extensions was unsatisfactory and the addition of combination chemotherapy is indicated.     

New strategies in the treatment of resectable non-small cell lung cancer

Non-small cell lung cancer is a systemic illness. Given the systemic nature of lung cancer, it seems that chemotherapy should play an essential role. In stage IIIA disease neoadjuvant chemotherapy plus surgical resection improves survival when compared with surgical resection alone. However, randomized trials using postoperative adjuvant chemotherapy with ‘older’ drugs has shown no substantial improvement in survival. Since new chemotherapeutic agents may provide additional benefits, there are various studies incorporating new agents in the resectable disease treatment setting. One focus for ongoing research is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I–II is feasible and appears not to compromise surgery. Another promising more individual approach is to tailor chemotherapy according to the pattern of genetic variants or abnormalities found in DNA and/or RNA extracted from the bloodstream. Furthermore, at present many types of new agents are available for testing as ‘consolidation treatment’ following induction treatment, including, angiogenesis inhibitors, antibodies to growth factor receptors, gene therapy and vaccines.     

Chemotherapy in NSCLC: historical review

The use of chemotherapy in patients with advanced NSCLC has been under investigation for several years. It has evolved from administration in the palliative care setting to integration into combined-modality curative therapy settings in patients with locoregionally-advanced disease. Following the largest meta-analysis in 1995 it was suggested that platinum-based chemotherapy was effective in treating patients with advanced disease. The absolute improvement in survival was 10% at 1 year and an increased median survival of 1.5 months. Since this analysis, platinum-based chemotherapy is considered the gold standard of treatment in this disease.     

Functional Organ Preservation in Locally Advanced Laryngeal Squamous Cell Carcinoma: Is there a Role for Induction Chemotherapy?

Concurrent chemoradiation (CRT) is currently the most effective strategy for organ preservation in locally advanced laryngeal squamous cell carcinoma (SCC) unsuitable for function-preserving surgery. The larynx preservation approach of induction chemotherapy followed by radiotherapy in responders is based on the hypothesis that tumours that show a satisfactory response to induction chemotherapy are more likely to respond to radiation-based treatment. This enables the use of chemotherapy response to identify patients who are more likely to achieve long-term disease control with organ-preserving therapies. An induction chemotherapy response allows prognostication, outcome prediction and treatment selection in patients with locally advanced laryngeal SCC. Excellent survival outcomes have been achieved with induction chemotherapy followed by CRT as definitive therapy in responders. The addition of docetaxel to cisplatin and 5-fluorouracil induction chemotherapy has also resulted in higher larynx preservation rates. Future organ preservation studies should assess whether induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by CRT in responders improves survival compared with an unselected approach of primary CRT in all eligible patients with T2 or T3 laryngeal SCC. The primary end point of such studies should be laryngo-oesophageal dysfunction-free survival, which focuses on the treatment goals of survival, disease control and laryngeal–oesophageal function after therapy. In addition, the inclusion of patients with N2 or N3 disease will help to determine whether the addition of docetaxel, cisplatin and 5-fluorouracil to CRT reduces the incidence of distant relapse in advanced laryngeal SCC. Other areas of interest include the use of concurrent cetuximab in place of platinum-based chemotherapy with radiotherapy in larynx preservation and the search for better predictive markers of successful larynx preservation than induction chemotherapy response.     

维持治疗在晚期结直肠癌化疗后达稳定患者中的价值及预后分析*

目的:探讨晚期结直肠癌姑息化疗后获得疾病稳定患者的预后异质性及个体化治疗策略的应用。方法:研究收集2008年4 月至2014年10月204 例在天津医科大学肿瘤医院接受标准一线和（或）二线化疗后获得疾病稳定的晚期结直肠癌患者,分析该人群临床病理特征,筛选预后异质性分层因子,并评估姑息化疗后治疗手段（即单纯观察或维持治疗）对于特殊人群的影响。结果:单因素生存分析表明化疗线数、基线CA724、CEA 、CA19- 9 水平、血小板淋巴细胞比率（PLR ）、姑息化疗后治疗手段为预后影响因素。多因素Cox 比例风险回归模型分析显示,一线化疗、基线CA19- 9 低水平、PLR 低水平、姑息化疗后维持治疗患者预后较好。亚组分析显示PLR 高水平患者中,维持治疗组与观察组无进展生存期分别为13.43个月和10.63个月（P = 0.003）。 结论:基线CA19- 9、PLR 水平及姑息化疗后治疗手段为获得疾病稳定的晚期结直肠癌患者的独立预后因子。疾病稳定人群尤其是PLR 高水平者宜接受维持治疗。      

New strategies in the treatment of resectable non-small cell lung cancer

Non-small cell lung cancer is a systemic illness. Given the systemic nature of lung cancer, it seems that chemotherapy should play an essential role. In stage IIIA disease neoadjuvant chemotherapy plus surgical resection improves survival when compared with surgical resection alone. However, randomized trials using postoperative adjuvant chemotherapy with 'older' drugs has shown no substantial improvement in survival. Since new chemotherapeutic agents may provide additional benefits, there are various studies incorporating new agents in the resectable disease treatment setting. One focus for ongoing research is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible and appears not to compromise surgery. Another promising more individual approach is to tailor chemotherapy according to the pattern of genetic variants or abnormalities found in DNA and/or RNA extracted from the bloodstream. Furthermore, at present many types of new agents are available for testing as 'consolidation treatment' following induction treatment, including, angiogenesis inhibitors, antibodies to growth factor receptors, gene therapy and vaccines.     

What’s new in Hodgkin’s lymphoma: ASH 2012 and more

Modern treatment strategies have resulted in an excellent overall survival in the majority of patients with Hodgkin’s lymphoma. PET-stratification is used to guide treatment in patients with limited disease in clinical trials, but recent results indicate that combined treatment with chemotherapy and radiotherapy is still the standard of care. Prediction of treatment related mortality and new data about chemotherapy induced infertility will guide our decisions especially in patients with advanced disease and brentuximab vedotin is now an approved option in patients with relapsed or refractory disease.     

Treatment of metastatic colorectal cancer

The treatment of metastatic colorectal cancer (mCRC) has become increasingly complex and nuanced as treatments have evolved over the last decade. During that time, treatment has evolved from single agent 5-fluorouracil (5FU) chemotherapy to combination chemotherapy, and more recently to the inclusion of monoclonal antibodies. As such, mCRC is evolving into a chronic disease in which the median overall survival (mOS) is in excess of 2 years and the 5-year survival is 10%. This review highlights the chemotherapy advances in the treatment of mCRC and focuses on the antibody therapies that have provided incremental improvements in survival. Additionally, we will discuss the management of resectable and unresectable liver metastases, and directed liver therapies. The treatment of metastatic colorectal cancer (mCRC) has become increasingly complex and nuanced as treatments have evolved over the last decade. During that time, treatment has evolved from single agent 5-fluorouracil (5FU) to combination chemotherapy and more recently the inclusion of monoclonal antibodies. As such, mCRC is evolving into a chronic disease in which the median overall survival (mOS) is in excess of 2 years and the 5-year survival is 10%. This review highlights the chemotherapy advances in the treatment of mCRC and focuses on the antibody therapies that have provided incremental improvements in survival. Additionally, we will discuss the management of resectable and unresectable liver metastases and directed liver therapies.