Lung Cancer

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.

A striking black-and-white photograph (see Figure) of nursing student Katherine Wilson, a nonsmoker who lived 5 years with small-cell lung cancer before dying in 2005 at age 28, won the Best of the United States first prize in the 2006 Lilly Oncology on Canvas: Expressions of a Cancer Journey International Art Competition and Exhibition. The US competition finale was held at the Metropolitan Pavilion, New York, with Lilly President and COO John C. Lechleiter, PhD, presenting the top three US finalists with their awards.

Bisphosphonates are an important part of managing bony metastasis of prostate, breast, lung, and other cancers but can cause osteonecrosis of the jaw (ONJ) in some patients.

In its second annual "Clinical Cancer Advances" report, the American Society of Clinical Oncology (ASCO) selected six notable developments in clinical cancer research as most important in 2006.

Taiwan-based researchers have defined and validated a set of five genes whose degree of expression in non-small-cell lung cancer (NSCLC) patients closely predicts their relapse-free and overall survival.

A retrospective review of 61 lung cancers identified during annual CT screening of high-risk individuals found that an exceptionally high rate of tumors may have been "overdiagnosed," particularly in women.

Results from Oncolytics Biotech's phase I trial of Reolysin, its oncolytic reovirus, show stable disease in 7 of 32 patients with advanced or metastatic solid tumors refractory to standard therapy or for which no curative standard therapy exists. Dr. Timothy Yap of The Institute of Cancer Research, Sutton, UK, presented the study at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

Postoperative radiotherapy, added to adjuvant cisplatin-based chemotherapy, resulted in a near-doubling of median survival in patients with completely resected non-small-cell lung cancer (NSCLC), compared with chemotherapy alone—but only in the presence of mediastinal lymph node involvement (N2 disease).

Pharmion Corporation has acquired Cabrellis Pharmaceuticals and gained US and European rights to amrubicin, a third-generation synthetic anthracycline currently in phase II trials for small-cell lung cancer in North America and Europe.

A device that displays a holograph-like 3-dimensional (3D) image, created from a CT, MRI, or PET dataset, holds promise for more accurate radiotherapy treatment planning (see image on page 1). James C. H. Chu, PhD, professor of radiation oncology, Rush University Medical Center, presented results of a pilot study of the Perspecta Spatial 3D System, developed by Actuality Systems, Inc. (Bedford, Massachusetts), at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology

Celebrating 20 years of providing practical reviews and peer commentaries to the oncology community in an effort to promote optimal cancer education and quality care for persons with cancer

The standard of care with regard to adjuvant chemotherapy of lung cancer has changed remarkably over the past 3 years. Until the initial report of the International Adjuvant Lung Trial in 2003, there was no real evidence from any individual randomized clinical trial (RCT) that adjuvant chemotherapy improves survival in resectable non-small-cell lung cancer. However, five RCTs that have now been reported indicate that adjuvant chemotherapy is effective, at least in certain subgroups of resectable patients. Moreover, numerous meta-analyses have also reported a positive effect from adjuvant treatment. Nonetheless, because of methodologic issues and conflicting results, the question of who should be treated and what constitutes optimal adjuvant therapy remains controversial. This article reviews the recent randomized trials that have contributed to a change in the state of the art, as well as some of the methodologic problems that may have confounded their proper interpretation. It also considers newer approaches to adjuvant therapy, with a particular focus on strategies that incorporate our growing knowledge of molecular medicine and predictive factors to the field of adjuvant chemotherapy of lung cancer.

The standard of care with regard to adjuvant chemotherapy of lung cancer has changed remarkably over the past 3 years. Until the initial report of the International Adjuvant Lung Trial in 2003, there was no real evidence from any individual randomized clinical trial (RCT) that adjuvant chemotherapy improves survival in resectable non-small-cell lung cancer. However, five RCTs that have now been reported indicate that adjuvant chemotherapy is effective, at least in certain subgroups of resectable patients. Moreover, numerous meta-analyses have also reported a positive effect from adjuvant treatment. Nonetheless, because of methodologic issues and conflicting results, the question of who should be treated and what constitutes optimal adjuvant therapy remains controversial. This article reviews the recent randomized trials that have contributed to a change in the state of the art, as well as some of the methodologic problems that may have confounded their proper interpretation. It also considers newer approaches to adjuvant therapy, with a particular focus on strategies that incorporate our growing knowledge of molecular medicine and predictive factors to the field of adjuvant chemotherapy of lung cancer.

The standard of care with regard to adjuvant chemotherapy of lung cancer has changed remarkably over the past 3 years. Until the initial report of the International Adjuvant Lung Trial in 2003, there was no real evidence from any individual randomized clinical trial (RCT) that adjuvant chemotherapy improves survival in resectable non-small-cell lung cancer. However, five RCTs that have now been reported indicate that adjuvant chemotherapy is effective, at least in certain subgroups of resectable patients. Moreover, numerous meta-analyses have also reported a positive effect from adjuvant treatment. Nonetheless, because of methodologic issues and conflicting results, the question of who should be treated and what constitutes optimal adjuvant therapy remains controversial. This article reviews the recent randomized trials that have contributed to a change in the state of the art, as well as some of the methodologic problems that may have confounded their proper interpretation. It also considers newer approaches to adjuvant therapy, with a particular focus on strategies that incorporate our growing knowledge of molecular medicine and predictive factors to the field of adjuvant chemotherapy of lung cancer.

A phase III multicenter study has confirmed thathigh tumor tissue expression of the geneERCC1 in patients with metastatic nonsmall-cell lung cancer (NSCLC) is predictiveof resistance to cisplatin.

Spiral CT screening of high-risk individuals could prevent about 80% of deaths from lung cancer, according to the latest results from the large collaborative I-ELCAP trial.

Avastin(bevacizumab, Genentech) has gainedFood and Drug Administration (FDA)approval in combination with carboplatinand paclitaxel for the first-line treatmentof unresectable, locally advanced, recurrent,or metastatic non-squamous-cell,non-small-cell lung cancer (NSCLC),which accounts for about three-quartersof newly diagnosed cases in the UnitedStates.

A blood test that measures specific blood proteins canaccurately distinguish lung cancer fromother smoking-related lung diseases, researchersfrom France said at the 31stCongress of the European Society forMedical Oncology (ESMO).

In a study investigating possible molecular abnormalities in nonsmokers with lung adenocarcinoma, a team of French researchers has found that never-smokers significantly overexpress the MAP (mitogen activated protein) kinases P38 and JNK (c-Jun N-terminal kinase), compared with smokers.

ZD6474 (Zactima), a once-daily oral drug that simultaneously blocks three tumor cell signaling pathways, looked promising in phase II studies vs gefitinib (Iressa) in advanced nonsmall- cell lung cancer (NSCLC) and can be combined with docetaxel (Taxotere), but the decision to move the drug into a phase III clinical trial triggered comments from the discussant (see Vantage Point) at the American Society of Clinical Oncology (ASCO) 42nd Annual Meeting.

Motexafin gadolinium (MGd, Xcytrin) combined with whole brain radiation therapy (WBRT) prolongs time to neurologic progression in non-small-cell lung cancer (NSCLC) patients with brain metastases if treatment starts within 3 weeks of the brain metastasis diagnosis, according to data from a phase III trial.

Pharmacyclics, Inc, announced that new data and analyses supporting the company's decision to file a new drug application (NDA) for motexafin gadolinium (Xcytrin) were presented at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO). This abstract was selected by the ASCO Scientific Program Committee to be featured in the "2006 Best of ASCO Meetings" in June.

Genentech, Inc, announced recently that the US Food and Drug Administration (FDA) has approved bevacizumab (Avastin) to be used in combination with carboplatin and paclitaxel chemotherapy for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small-cell lung cancer (NSCLC), the most common type of lung cancer.