Lung Cancer

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.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.

On October 20, 2006, the International-Early Lung Cancer Action Program (I-ELCAP), an international consortium of leading early lung cancer detection researchers and allied health-care providers including radiologists, thoracic surgeons, pulmonologists, oncologists, statisticians, research nurses, and computer scientists

On April 21, 2005, the Cancer Research and Prevention Foundation (CRPF), in conjunction with academic researchers, federal scientists, lung cancer advocates, and representatives of a number of pharmaceutical and diagnostic imaging companies, participated in a workshop held in Annapolis, Md, on the development of high-resolution spiral computed tomography (CT) imaging tools to assess therapeutic response in lung cancer clinical trials. In this report, we will address developments that led up to that workshop, what was discussed, and recommendations that came out of the meeting.

The science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.

a brief overview of the dosing and administration guidelines for the various targeted therapy agents discussed in this supplement to the ONCOLOGY Nurse Edition. Please consult the manufacturer's package insert for more information.

Primary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal status. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of local failure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.

A recombinant fusion protein designed to stimulate immune response against the MAGE-A3 tumor antigen has shown some efficacy in patients with completely resected early-stage non-small-cell lung cancer (NSCLC), decreasing the recurrence rate by about one-third.

Use of adjuvant chemotherapy for stage IB non-small-cell lung cancer (NSCLC) is less certain than it appeared to be at last year's American Society of Clinical Oncology (ASCO) meeting, according to a study reported at the 2006 ASCO Annual Meeting.

A new bioengineered protein that targets two apoptosis receptors produced one dramatic tumor regression and stopped tumor growth in several cases of disease stabilization in 60% of the advanced cancer patients treated in a phase I dose-finding trial

Researchers are using large patient datasets and computer programs to develop an expanded cancer staging system, moving beyond the conventional three markers—tumor size, nodal involvement, and metastasis—used in TNM staging. The new system, presented at the International Union Against Cancer's World Cancer Congress, uses TNM stage and other factors, such as histology and tumor grade, to fine tune and personalize prognosis

A systematic approach to early treatment of skin toxicity in patients on erlotinib (Tarceva)-based therapy can reduce the need for dose modification or delay in patients with head and neck cancer or non-small-cell lung cancer (NSCLC)

A vaccine that blocks production of transforming growth factor-beta 2 (TGF-β2) extended 1-year survival in patients with advanced non-small-cell lung cancer (NSCLC)

Brain, lung, and ovarian cancers have been chosen as the first cancers to be studied in the pilot phase of The Cancer Genome Atlas (TCGA) project

 I read with great interest the paper by Michael Brave and colleagues from the US Food and Drug Administration (FDA). The authors describe the FDA's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer. This decision was made after a Gynecologic Oncology Group trial (GOG-0179) conducted at 94 American study centers demonstrated a survival benefit in patients with stage IVB, recurrent, or persistent carcinoma of the cervix who received cisplatin plus topotecan (Hycamtin) compared with those who received cisplatin alone.

Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.

Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.