Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past,the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

Current status of adjuvant therapy in patients with colorectal cancer: report and commentary on the Consensus Conference, 16-18 April 1990, National Cancer Institute, Bethesda, Maryland]

This is a report on the Consensus Development Conference on adjuvant therapy for patients with colorectal carcinoma, which was held at the National Cancer Institute of the National Institutes of Health (NIH) in Bethesda, Maryland between April 16th and 18th 1990. Based on statistically significant results of a clinical trial adjuvant therapy with 5-fluorouracil (5-FU) and levamisole was recommended outside controlled clinical studies for patients with Dukes C colon carcinoma, but because no optimal form of adjuvant therapy yet exists there is still the need for further trials. No recommendations were given for patients with Dukes B colon carcinoma. For patients with Dukes B + C rectal cancer combined radiation therapy and 5-FU-based chemotherapy was considered "standard therapy" according to the consensus panel, but this recommendation seems to be still worth discussing. Since there is need of further evaluation of newly-recognized prognostic factors and also to optimize adjuvant strategies the panel stated that further prospective randomized studies are warranted. Hence, the establishment of a multicentre study group also in Austria appears to be an essential application of such trials in order to contribute towards ameliorating the prognosis of patients with colorectal carcinoma.     

NSABP breast cancer clinical trials: recent results and future directions

Over the past 40 years, the National Surgical Adjuvant Breast and Bowel Project (NSABP) has conducted several large, randomized clinical trials evaluating various aspects of surgical and adjuvant therapy in patients with operable breast cancer. Results from these trials have contributed significantly in reducing the extent of surgical procedures and in improving the outcome of patients with early-stage breast cancer. Furthermore, they have helped to establish standards of care for the surgical management of invasive and non-invasive disease and for the use of adjuvant hormonal therapy and adjuvant chemotherapy for patients with negative as well as for those with positive axillary nodes. More recent trials are evaluating several new classes of promising drugs such as the aromatase inhibitors in postmenopausal women with invasive or intraductal breast cancer, the taxanes for patients with positive nodes and in the neoadjuvant setting and other targeted molecular therapies such as trastuzumab and bisphosphonates. Results from these ongoing and recently completed trials could improve outcomes and quality of life for patients with early-stage breast cancer.     

The evolving role of endocrine therapy for breast cancer

The indirect comparison of LHRH agonist with tamoxifen showed similar efficacy in the adjuvant treatment of premenopausal endocrine-responsive breast cancer patients. Furthermore, LHRH agonist is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy. Data concerning combination of LHRH agonist with third-generation aromatase inhibitors are still lacking. Moreover, duration of therapy with LHRH agonist is still a matter of debate. In randomized clinical trials, each of the third-generation aromatase inhibitors (AIs) has demonstrated efficacy in the adjuvant treatment of postmenopausal women with receptor' -positive tumors. Anastrozole has been shown to improve disease-free survival when compared with tamoxifen, letrozole has been shown to further reduce the rate of breast cancer events when given as extended adjuvant therapy in women completing between 4.5 and 6 years of tamoxifen, and exemestane has been shown to improve disease-free survival when substituted for tamoxifen after an initial 2-3 years of adjuvant therapy. Although long-term follow-up for safety and overall survival continues in each of these trials, currently available data suggest that an AI should now be included as part of adjuvant endocrine therapy for the great majority of receptor-positive postmenopausal patients.     

Adjuvant chemotherapy in oesophageal cancer: a meta-analysis and experience from the Shanghai Cancer Hospital

Whether adjuvant chemotherapy increases survival of oesophageal cancer patients has been widely debated. The present study used meta-analysis software to combine data from six studies up to July 2007 that were found and selected as suitable, comprising a total of 1001 oesophageal cancer patients. The results indicated that adjuvant chemotherapy did not significantly improve outcome in oesophageal cancer patients. A trend towards improved outcome from adjuvant chemotherapy was found in lymph node-positive patients, but did not reach significance. In our own study including 270 oesophageal cancer patients, adjuvant chemotherapy did not improve overall patient survival, but did improve survival for patients with metastases in cervical and/or celiac lymph nodes (stage IVa). Although our study had the largest patient sample, more prospective clinical trials with large numbers of patients are necessary to confirm the value of adjuvant chemotherapy in stage IVa patients.     

Postoperative adjuvant therapy for premenopausal patients with breast cancer

The age peak of breast cancer morbidity is younger in Japan in comparison with that in Western countries. This results in a higher incidence of premenopausal patients in Japan. There are specific concerns on the postoperative adjuvant therapy for premenopausal patients, such as its influences on pregnancy, delivery and lactation, and acute and chronic adverse events related to earlier ovarian dysfunction. International guidelines such as the recommendations by the St. Gallen consensus conference provide clinicians with useful information on the risk assessment for recurrence and treatment selection of postoperative adjuvant therapy. Recommendations on postoperative adjuvant therapy for premenopausal breast cancer patients are presented according to the guidelines and evidence established by clinical trials. On-going clinical trials to resolve unanswered questions on the adjuvant therapy are also reviewed. Finally, future perspectives on the adjuvant therapy are discussed.     

Evidence-based guidelines for adjuvant therapy for resected adenocarcinoma of the pancreas

Pancreatic cancer, the fourth most common cause of cancer deaths, has a five-year survival rate of 5% or less. Surgical removal of the tumor may improve survival, but survival remains poor even in optimally resected patients. The best adjuvant therapy for patients with resected pancreatic cancer is not clear. Surgical resection followed by chemoradiation and maintenance chemotherapy has been considered the most beneficial treatment for improving survival, but more recent studies have suggested that chemotherapy alone is more effective. The purpose of this article is to review randomized controlled studies of adjuvant chemoradiation or chemotherapy alone in the treatment of resected pancreatic cancer and to determine the optimal adjuvant therapy after curative resection with negative or microscopically positive margins. The outcomes of interest were overall survival and disease-free survival. The results indicate that chemoradiation is an acceptable option for adjuvant treatment. Three of the four randomized controlled trials suggest that adjuvant chemoradiation for resected pancreatic cancer improves overall survival. Adding gemcitabine to the chemoradiation regimen also confers increased disease-free survival. Providers counseling patients regarding treatment options for resected pancreatic cancer should continue to recommend adjuvant therapy--a combination of chemotherapy including gemcitabine and radiotherapy--for appropriately selected patients.     

平消胶囊用于肿瘤协同治疗的临床证据

目的 系统检索平消胶囊用于肿瘤协同治疗的临床证据,以期为临床应用提供参考.方法 计算机检索CBM、CNKI、VIP、WanFang Data和MEDLINE数据库,检索时限均为从建库至2013年2月,查找平消胶囊用于肿瘤协同治疗的随机和非随机临床对照研究,而后分病种进行证据综述.结果 共检出文献1 097篇,最终纳入随机对照研究41篇,非随机对照研究15篇.现有证据显示:平消胶囊已用于多种肿瘤的协同治疗,可提高放化疗疗效,降低放化疗毒副反应,且能提高患者生存质量.结论 当前证据显示,在放化疗的基础上,应用平消胶囊辅助治疗肿瘤,其疗效和安全性优于单纯放化疗.但由于纳入研究质量有限,上述结果仍需进一步高质量研究验证.     

Targeted therapy in colorectal cancer

Advances in chemotherapeutic agents have led to improved outcomes for patients with metastatic colorectal cancer (CRC). Chemotherapies, however, are limited by their toxicities and lack of specificity. Aberrations in the regulation and expression of growth factors have been implicated in the development of CRC, and this understanding has led to the development of targeted agents. In 2004, two novel agents, bevacizumab and cetuximab, were approved by the US Food and Drug Administration for the treatment of metastatic CRC. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, and cetuximab, a human-mouse chimeric monoclonal antibody to the epidermal growth factor receptor, have changed the field dramatically. Bevacizumab appears to augment the efficacy of combination chemotherapy regimens for the treatment of metastatic CRC in both the first- and second-line settings, and the role of bevacizumab as part of adjuvant treatment is the subject of ongoing trials. However, because of the increased incidence of serious arterial thromboembolic events, gastrointestinal perforations, bleeding complications, and hypertension associated with bevacizumab, this agent is probably not indicated in all circumstances. Combination treatment with cetuximab and irinotecan appears appropriate in patients with advanced CRC who have failed irinotecan. Patients who are unable to receive additional irinotecan may be treated with cetuximab monotherapy. Positive epidermal growth factor receptor status by immunohistochemistry of a tumor specimen is presently mandated to determine candidacy for this therapy, although this assay appears to be suboptimal and newer assessment techniques to determine suitability for therapy must be developed. Phase III trials should shed light on the role of cetuximab in the first-line metastatic and adjuvant settings. Multitargeted strategies in CRC combining chemotherapy with bevacizumab and cetuximab are currently being explored. Further advances in the treatment of CRC are expected through continued scientific investigation and well-designed clinical trials.     

Current status of local therapy in malignant gliomas — A clinical review of three selected approaches

Malignant gliomas are the most frequently occurring, devastating primary brain tumors, and are coupled with a poor survival rate. Despite the fact that complete neurosurgical resection of these tumors is impossible in consideration of their infiltrating nature, surgical resection followed by adjuvant therapeutics, including radiation therapy and chemotherapy, is still the current standard therapy. Systemic chemotherapy is restricted by the blood–brain barrier, while methods of local delivery, such as with drug-impregnated wafers, convection-enhanced drug delivery, or direct perilesional injections, present attractive ways to circumvent these barriers. These methods are promising ways for direct delivery of either standard chemotherapeutic or new anti-cancer agents. Several clinical trials showed controversial results relating to the influence of a local delivery of chemotherapy on the survival of patients with both recurrent and newly diagnosed malignant gliomas. Our article will review the development of the drug-impregnated release, as well as convection-enhanced delivery and the direct injection into brain tissue, which has been used predominantly in gene-therapy trials. Further, it will focus on the use of convection-enhanced delivery in the treatment of patients with malignant gliomas, placing special emphasis on potential shortcomings in past clinical trials. Although there is a strong need for new or additional therapeutic strategies in the treatment of malignant gliomas, and although local delivery of chemotherapy in those tumors might be a powerful tool, local therapy is used only sporadically nowadays. Thus, we have to learn from our mistakes in the past and we strongly encourage future developments in this field.     

一例ⅡB期非小细胞肺癌术后患者的循证治疗

目的报告1例ⅡB期非小细胞肺癌术后患者的循证治疗体会。方法将针对该例患者临床问题转化为可回答的形式,通过计算机检索Cochrane图书馆（2009年第2期）、PubMed（1970～2009年6月）和ACP Journal Club（1996～2009年6月）,查找并评价当前与非小细胞肺癌ⅡB期治疗相关的最佳临床证据。结果现有证据表明,第Ⅰ、Ⅱ期术后辅助性放疗、化疗并不能改善患者生存率,反而会相对增加患者的死亡风险。按照患者及家属意愿,该患者术后未进行放化疗,而是采用姑息对症支持治疗,效果满意,好转出院。结论Ⅰ、Ⅱ期非小细胞肺癌术后放疗或化疗并不能明显改善患者生存率,反而会相对增加患者的死亡风险。因而,术后是否采用放疗或化疗应慎重考虑。     

Technology evaluation: edrecolomab, Centocor Inc

Specific targeting of tumor cells may be achieved by using monoclonal antibodies to tumor antigens. Edrecolomab is a mouse-derived monoclonal IGg2A antibody directed against the human tumor-associated CO17-1A (or Ep-CAM) antigen, and is the first monoclonal antibody approved for cancer therapy. Encouraging results of several clinical trials were recently reported using edrecolomab for adjuvant therapy after surgery of Duke's C colorectal cancer. Side effects and toxicity profiles compare favorably to conventional regimens of radio- or chemotherapy. Future challenges lie in further improvement of these novel therapeutics, hopefully generating benefit for a larger number of cancer patients.     

Malignant melanoma

There have been many prospective randomized clinical trials of IFNalpha as post-surgical adjuvant therapy for high-risk melanoma patients. High dose IFNalpha therapy(HDI) has been reported to be effective in disease-free survival (DFS). However, the usefulness of HDI therapy is still controversial due to its grave toxicity. Low dose IFNalpha therapy (LDI) has no consistent effects on DFS. Most trials showed little activity in patients with metastatic melanoma. In Japan, IFNbeta, in combination with chemotherapy, has been used as post-surgical adjuvant therapy, and has been considered to improve the prognosis of stage III melanoma patients. In addition, we have recently performed a phase I/IIa trial of IFNbeta gene therapy for advanced melanoma patients.     

Managing high-risk breast cancer

OBJECTIVES: To identify breast cancer patients at high risk for recurrence. To describe current evidence for clinical management of early and locally advanced breast cancer and integrate this knowledge into nursing practice. DATA SOURCES: Articles, abstracts, and practice guidelines. CONCLUSION: Recent clinical trials have integrated the biology of breast cancer into individualized systemic therapy. Risk-adjusted treatment is driven by the addition of taxane therapy to systemic therapy, aromatase inhibitors, and trastuzumab into adjuvant therapy strategies. IMPLICATIONS FOR NURSING PRACTICE: The decision to initiate systemic adjuvant therapy requires knowledge of risk of relapse, integration of evidence from clinical trials, and facilitation of patient decision-making.     

Meta-analysis of adjuvant immunochemotherapy using OK-432 in patients with resected non-small-cell lung cancer

The benefits of immunochemotherapy with a penicillin-treated, lyophilized preparation of Streptococcus pyogenes, OK-432 (Picibanil), were reassessed in patients with resected non-small-cell lung cancer through a meta-analysis based on data from 1,520 patients enrolled in 11 randomized clinical trials. All 11 trials were started before 1991, and the subjects had been followed up for at least 5 years after surgery and randomization. In these trials, standard chemotherapy was compared with the same therapy plus OK-432. The endpoint of interest was overall survival, and analysis was based on intent-to-treat population without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 5-year survival rate for all eligible patients in the 11 trials was 51.2% in the immunochemotherapy group versus 43.7% in the chemotherapy group. The odds ratio (OR) for overall survival was 0.70 (95% CI = 0.56-0.87, p = 0.0010). Analysis of four trials in which central randomization was performed also reconfirmed a significantly longer survival time for the immunochemotherapy group (OR = 0.66, 95% CI = 0.44-1.00, p = 0.049). Based on these results of meta-analysis, it is postulated that postoperative adjuvant immunochemotherapy using OK-432 might improve the survival of patients after resection of non-small-cell lung cancer.     

Tumor-associated proteolytic factors uPA and PAI-1: critical appraisal of their clinical relevance in breast cancer and their integration into decision-support algorithms

This review considers the past, present, and projected future clinical relevance of the serine protease urokinase-type plasminogen activator (uPA), and its inhibitor, plasminogen activator inhibitor-type 1 (PAI-1), in breast cancer. These factors play a key role in tumor invasion and metastasis in many cancers. In primary breast cancer, their prognostic and predictive impact has been validated at the highest level of evidence by a multicenter therapy trial (Chemo N0) and a large European Organisation for Research and Treatment Cancer-Receptor and Biomarker Group EORTC RBG pooled analysis (n = 8377). The greatest clinical use is in node-negative breast cancer, where the test can avoid over-treatment by adjuvant chemotherapy in patients with non-aggressive disease. In intermediate-risk patients as defined by the international St. Gallen consensus, it can be used to identify patients who should receive chemotherapy because their tumor is more aggressive than classical pathological factors would suggest. Gene expression signatures are already being used in clinical trials to define the population of patients with breast cancer who should receive chemotherapy. The decision for treatment ignores the highly validated information that could be provided by uPA/PAI-1. A current and future challenge is to integrate the information provided by tumor biological factors, particularly uPA/PAI-1, into refined risk assessment and decision support algorithms incorporating gene expression signatures. This article describes a paradigm ("marker fusion") for doing so and a bioinformatics approach based on this paradigm. This concept could be useful in assessing and maximizing the performance of risk assessment and the quality of therapeutic indications.     

BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma.

Results of our study suggest that BCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. BCG is more effective in patients with small amounts of subclinical disease. It is apparent from results of clinical trials that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. Hwever, until clinical trials are complete, this treatment as adjuvant therapy must be considered investigational.     

外源性褪黑素对肿瘤辅助治疗效果的Meta分析

目的 系统评价肿瘤患者进行化疗或放疗时,采用褪黑素进行辅助治疗的有效性和安全性.方法 计算机检索MEDLINE(1980～2010.1)、Cochrane图书馆(2009年第4期)、万方数据库(1980～2010.1)、VIP(1980～2010.1)、CNKI(1980～2010.1)、ELSEVIER Scienc...     

Chemotherapie beim Prostatakarzinom

For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists.