Lung Cancer

Over the past decade, studies have shown improved survival inpatients with locally advanced non–small-cell lung cancer. This can beattributed to better systemic therapy, growing experience with combined-modality therapy, technologic advances allowing for increasedradiation doses, better supportive care, and better patient selection.With longer survival, we are seeing an increase in the incidence ofcentral nervous system (CNS) metastases. Prophylactic cranial irradiation(PCI) decreases the incidence of CNS metastases in these patientsand may have a favorable impact on quality of life and overall survival.This paper reviews the incidence of CNS metastases in non–small-celllung cancer patients, past experience with PCI, and a current studyevaluating the impact of PCI on survival, neuropsychological function,and quality of life.

Areport focused on women [andsmoking] is greatly neededNo longer are the first signsof an epidemic of tobacco-related diseasesamong women being seen, aswas the case when the [first such reportfrom the US Surgeon General in1980] was written. Since 1980, hundredsof additional studies have expandedwhat is known about the healtheffects of smoking among women, andthis report summarizes that knowledge.Today the nation is in the midst of afull-blown epidemic. Lung cancer,once rare among women, is now theleading cause of female cancer deathin this country, accounting for 25% ofall cancer deaths among women.

Drs. Novello and Le Chevalierhave reviewed the subject ofchemotherapy for non–smallcelllung cancer (NSCLC) in greatdetail, organized under numerous subheadings.I will systematically commenton each section of this excellentoverview, which deals with most ofthe published or recently presenteddata on the subjects discussed. Insome cases, trials of multimodalitytherapies, and not just chemotherapy,are included in the review.

The prognosis of patients with advanced non–small-cell lung cancer(NSCLC) remains poor. Systemic chemotherapy prolongs survivalin this group of patients and palliates symptoms compared to bestsupportive care alone but more effective therapeutic strategies areneeded. Novel agents that selectively target biological pathways oftumor growth offer hope of improving response and survival ratesbeyond what has been achieved with standard cytotoxic chemotherapy.Part 2 of this two-part article addresses the role of chemotherapy inlocally advanced and advanced NSCLC, including the use of novelagents, considerations in elderly patients, and studies of second-linetreatment.

Drs. Novello and Le Chevalierhave written a comprehensivereview on the role of chemotherapyin the treatment of non–smallcelllung cancer (NSCLC). Theirreview spans chemotherapy’s controversialuse in early-stage disease toits mainstream use in late-stage disease.The authors highlight the controversiesin the treatment andresearch of all stages of NSCLC anddiscuss ongoing research in combiningchemotherapy with the new molecularlytargeted agents.

Drs. Novello and Le Chevalierhave produced a comprehensivesummary of a large numberof trials of chemotherapy for allstages of non–small-cell lung cancer(NSCLC). This is a broad subjectarea, constantly changing and rifewith controversy; selecting the keytrials with international relevance isno small feat. Nonetheless, the reviewhighlights many salient issuesin the treatment of lung cancer.

Non–small-cell lung cancer (NSCLC) accounts for approximately80% of all lung tumors. Patients diagnosed with early-stage diseasegenerally undergo surgery, but up to 50% develop local or distantrecurrences. The benefit of chemotherapy in this disease is modest, butnew drugs and combined strategies offer hope of improved survivalrates. Because the disease recurs outside the chest in 70% of cases, oneof the foremost goals of therapy is to prevent distant dissemination. Tothis end, chemotherapy may be administered preoperatively or afterresection of the tumor. The first part of this article, which concludesnext month, will address adjuvant and neoadjuvant chemotherapy inearly-stage non–small-cell lung cancer.

HOUSTON-Introgen Therapeutics, Inc. has published data from its phase II study combining Advexin, an adenoviral vector containing the p53 tumor-suppressor gene, with radiation therapy in patients with nonmetastatic non-small-cell lung cancer (NSCLC) (Clinical Cancer Research, January 2003). The patients were ineligible to receive surgery or combination therapy with radiation and chemotherapy.

Small-cell lung cancer is an aggressive tumor associated with highrates of regional or distant metastases at diagnosis. Although highlychemosensitive to agents given in the first-line setting (eg, etoposideand cisplatin), most patients relapse and have a poor prognosis.Treatment options for relapsed patients include radiotherapy forlimited-stage disease and chemotherapy or combined modalities foradvanced-stage disease. In clinical practice, however, some oncologistsmaintain that chemotherapy provides an insufficient survivalbenefit to justify the sometimes debilitating toxicity associated with themore active regimens in particular. Other potential barriers to furthertreatment include patient comorbidities, performance status, site(s) ofprogression, progression-free interval, and previous treatments. However,numerous clinical trials demonstrate that some patients benefitfrom treatment, achieving prolonged survival, symptom palliation,improved quality of life, and the opportunity, albeit rare, for durableremission. Additionally, several novel chemotherapeutics are availablethat alone or in combination help patients lead an improvedquality of life. Finally, alternative routes and schedules-oral formulations,weekly administration, and prolonged treatment vacations-have been developed to deliver chemotherapy to patients with poorperformance status or multiple comorbidities. This article reviews theadvantages and disadvantages of treating recurrent small-cell lungcancer and summarizes the utility of several active agents.

In this issue of ONCOLOGY, Dr.John Eckhardt provides an excellentreview of the challenge oftherapy for patients with small-celllung cancer (SCLC) who relapse afterfirst-line therapy. Dr. Eckhardt outlinesthe prognostic factors influencingresponse to second-line treatment,survival, and treatment-related toxicity.These prognostic factors includethe response to first-line therapy, theprogression-free interval, and performancestatus. The influence of the chemotherapyregimen and the durationof treatment on symptom palliationand quality of life are also discussed.Dr. Eckhardt provides an excellentsummary of the activity of multipleagents in the second-line setting.

NEW YORK-The investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (Tarceva, also known as OSI-774) produced objective remissions and mild toxicity in stage IV non-small-cell lung cancer (NSCLC) patients who had undergone a number of prior chemotherapy regimens, according to results of a phase II study.

Small-cell lung cancer (SCLC)poses one of the greatest managementchallenges in clinicaloncology, as the mortality rate approaches95% within 2 years afterpresentation for patients with extensivedisease, despite widespread useof combination chemotherapy.[1]Given a disease that is largely managedby the community physician andfor which recent definitive clinicaltrials are relatively scarce,[2] it isincumbent upon the clinician to becognizant of the critical factors innostudies suggesting that three-drugcombinations are indicated.

BRIDGEWATER, New Jersey-The US Food and Drug Administration (FDA) has approved Taxotere (docetaxel, Aventis) as first-line therapy, in combination with cisplatin (Platinol), in patients with unresectable, locally advanced or metastatic non-small-cell lung cancer (NSCLC).

ROCHESTER, Minnesota-In a Mayo Clinic study of low-dose helical CT screening for lung cancer, nearly 70% of the study participants had one or more suspicious lung nodules, but only 1.4% of all nodules proved to be malignant. The other 98.6% were benign "and therefore were false-positive findings," said lead investigator Stephen J. Swensen, MD, professor of radiology. The results, he said, offer reasons for optimism as well as reasons for doubt that CT screening for lung cancer will ultimately save lives by reducing disease-specific mortality.

NEW YORK- A combination of vinorelbine (Navelbine) and gemcitabine (Gemzar) showed similar efficacy to the standard platinum-based regimen for advanced non-small-cell lung cancer (NSCLC) and a different toxicity profile in a phase II study presented at the Mount Sinai School of Medicine Chemotherapy Foundation Symposium XX.

Drs. Basche and Kelly presentan excellent comprehensivereview of the treatment ofnon–small-cell lung cancer in olderpersons. Articles such as this, whichfocus on the older patient, are of paramountimportance for several reasons.First, cancer is a disease ofaging, with an 11-fold increased incidenceand a 16-fold increase in cancer-related mortality among patientsover age 65 compared to those under65.[1] Second, the population is aging,and in the year 2030, approximately22% will be over 65.[1] Third,data on older cancer patients are limitedsecondary to an underrepresentationof this population in clinicaltrials.[2,3] Based on these facts, acomprehensive review of the availabledata is important, especially toguide future research.

The importance of cancer as aproblem in the elderly is gainingincreasing appreciationdue, in part, to the demographicchanges taking place in this countryand around the world and their associationto the incidence of cancer.Ongoing epidemiologic research overthe past several decades has consistentlyconfirmed the continuing trendtoward an aging population. In theUnited States, an anticipated 20.1%of the population will be 65 years ofage or older by 2030, the number ofpeople 75 years of age or older willhave tripled, and the 85-or-older agegroup will have doubled.[1]

WASHINGTON-The failure of most states to put the money they receive from the Master Settlement Agreement with the tobacco industry into tobacco-control programs will increase their future health care costs for lung cancer and other tobacco-related illnesses, according to two nonprofit health groups. An independent analysis of data published in October 2002 found that states with the highest incidence of lung cancer generally spent the least amount of money for tobacco control.

The majority of individuals diagnosed with lung cancer in theUnited States are 70 years of age and older. Defining appropriatetherapy for older patients with non–small-cell lung cancer (NSCLC) isbecoming a major focus of clinical research. In this article, we reviewthe available data on clinical predictors of risk and benefit for elderlyNSCLC patients receiving treatment via a variety of modalities, includingsurgery, radiotherapy, combined radiotherapy and chemotherapy,and chemotherapy alone. The data demonstrate that subgroups ofelderly patients benefit from appropriately selected treatment. Participationof older patients in clinical trials designed to assess efficacy,toxicity, and quality-of-life outcomes for recently developed treatmentmodalities in this population is critical.

NEW YORK-Computed tomography (CT) screening for lung cancer has revealed subtypes of nodules whose natural histories are being assessed in long-term follow-up, according to Claudia I. Henschke, PhD, MD, director, Division of Chest Imaging, and professor of radiology, Weill Medical College, Cornell University.

ORLANDO - About half of the new cases of lung cancer diagnosed each year occur in patients who have already quit smoking. Treatment with oral doses of 9-cis-retinoic acid (9cRA), a form of vitamin A, might help protect ex-smokers from previous damage done to their lungs, said Jonathan M. Kurie, MD, Thoracic and Head and Neck Medical Oncology, M.D. Anderson Cancer Center.

BETHESDA, Maryland-Researchers have begun accruing 50,000 patients for the National Lung Screening Trial (NLST), the much-awaited comparison of the efficacy of spiral CT scans and chest x-rays in reducing lung cancer mortality. Investigators in the 8-year, National Cancer Institute-supported study expect to complete enrollment within 2 years. Enrollment will be aided by a $5 million educational campaign funded and organized by the American Cancer Society (ACS), and aimed at encouraging current and former cigarette smokers to participate in the trial.

SILVER SPRING, Maryland-The Oncologic Drugs Advisory Committee (ODAC) has essentially recommended that the US FDA grant accelerated approval to Iressa (gefitinib, AstraZeneca) for the oral treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC) in patients who have previously received platinum-based chemotherapy regimens.

WASHINGTON-An assessment by the US Environmental Protection Agency’s National Center for Environmental Assessment concludes that long-term inhalation of diesel engine exhaust "is likely to pose a lung cancer hazard to humans, as well as damage the lung in other ways, depending on exposure."

ORLANDO-Weekly docetaxel (Taxotere) combined with gemcitabine (Gemzar) is a useful doublet in circumstances in which a platinum-containing doublet is not desirable in the treatment of advanced non-small-cell lung cancer (NSCLC), according to the ACORN 9901 multicenter trial. Ravindrath Patel, MD, of the Comprehensive Blood and Cancer Institute, Bakersfield, California, presented the data at a poster session of the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1276).

n ROCKVILLE, Maryland-The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 3 that phase II results of AstraZeneca Pharmaceuticals’ EGFR tyrosine kinase inhibitor Iressa (ZD1839, gefitinib) as third-line therapy for advanced non-small-cell lung cancer (NSCLC) were "reasonably likely to predict clinical benefit." The FDA considers this a recommendation for accelerated approval. Look for a complete report of the ODAC decision and a review of the phase II trials of Iressa in NSCLC in next month’s issue of ONI.

HORSHAM, Pennsylvania-Cell Pathways, Inc. has announced that the National Cancer Institute is sponsoring two phase II studies of the company’s investigational drug Aptosyn (exisulind) in combination therapies for lung cancer. The Cancer and Leukemia Group B (CALGB) is studying Aptosyn in combination with eto-poside (VePesid) and carboplatin (Paraplatin) in patients with extensive-stage small-cell lung cancer. The Eastern Cooperative Oncology Group (ECOG) is investigating Aptosyn in combination with gemcitabine (Gem-zar) and carboplatin in patients with advanced non-small-cell lung cancer.

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

For more than 2 decades, combination chemotherapy has been the standard treatment for patients with small-cell lung cancer. Despite high initial response rates in both extensive- and limited-stage disease, long-term survival

Lung cancer is the leading cause of cancer-related death in the United States. There was rapid progress in the treatment of lung cancer during past decades, but local control and survival rates are still poor.