Lung Cancer

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

BETHESDA, Maryland—Newly released data show that the nation’s mortality rate for all cancers combined, which declined between 1994 and 1998, remained stable from 1998 through 2000. However, the mortality rate for the four leading malignancies in the United States—lung, female breast, prostate, and colorectal—continued to decline in the late 1990s, according to the "Annual Report to the Nation on the Status of Cancer, 1975-2000."

CHICAGO—Gefitinib (Iressa) produced clinically meaningful improvement in disease-related symptoms in advanced non-small-cell lung cancer (NSCLC), David F. Cella, PhD, reported at the 39th Annual Meeting of the American Society of Clinical Oncology (abstract 2531). Dr. Cella is professor, Northwestern University, and director, Center on Outcomes, Research and Education (CORE), Evanston Northwestern Health-care, Evanston, Illinois. The study was supported by AstraZeneca.

VANCOUVER, Canada-A tri-modal regimen integrating surgical resection with concurrent chemotherapy and radiation (CT/RT) in non-small-cell lung cancer (NSCLC) continued to show benefits in an updated analysis of Intergroup Trial 0139 presented at the 10th World Conference on Lung Cancer plenary session (abstract PL-4). Kathy Albain, MD, who gave the initial report at ASCO 2003 (abstract 2497), presented the updated results.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement toOncology News International presents11 reports on novel agents targetingHER1/EGFR, VEGF, and HER2/neu receptorsin the treatment of non–small-cell lung cancer,colorectal cancer, mesothelioma, andglioblastoma. The reports summarizeselected presentations from theAmerican Society of Clinical Oncology (ASCO)39th Annual Meeting and a satellitesymposium held in conjunction with ASCO.

This special supplement to Oncology News International includes 28 reportswith updated information on clinical trials investigating capecitabine and other agents inthe treatment of advanced colorectal and breast cancers, and other solid tumors.The reports summarize selected presentations from the 39th Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) and related educational symposiaheld in conjunction with ASCO.

ASCO—Adjuvant cisplatin (Platinol)-based chemotherapy significantly improved survival in patients with completely resected non-small-cell lung cancer (NSCLC), Thierry Le Chevalier, MD, reported at the plenary session of the 39th Annual Meeting of the American Society of Clinical Oncology (abstract 6). Dr. Le Chevalier, professor of medicine, Gustav-Roussy Institute, Villejuif, France, concluded that adjuvant chemotherapy could be recommended and might prevent 7,000 deaths worldwide from NSCLC every year. The International Adjuvant Lung Cancer Trial (IALT), which included 1,867 patients treated in 148 centers in 33 countries across five continents, showed that chemotherapy conferred a 4.1% absolute benefit in overall survival and a 5.1% absolute benefit in disease-free survival after 5 years.

Dr. Kelly has written an excellentarticle demonstrating theclinical significance of achievingstable disease in advanced non–small-cell lung cancer (NSCLC)patients. This hypothesis is supportedby clinical data from two phase IItrials (Iressa Dose Evaluation in AdvancedLung Cancer [IDEAL-1 andIDEAL-2]) of the epidermal growthfactorreceptor (EGFR) inhibitor gefitinib(ZD1839, Iressa) in previouslytreated patients. She appropriatelypoints out that although tumor shrinkageis a conventionally used end pointfor cytotoxic drugs, it may not be appropriatefor the “novel” cytostaticagents. For these agents, stabilizationof disease without obvious tumorshrinkage may result in a clinicalbenefit.

Dr. Karen Kelly has written atimely discussion on the clinicalbenefit of achieving stabledisease in advanced non–smallcelllung cancer (NSCLC). The goalsof current therapy are to palliate symptoms,optimize quality of life (QOL),and prolong survival. It is argued thattumor shrinkage may not be mandatoryto achieve these goals, particularlyin the evaluation of moleculartargeted therapies that may be cytostaticrather than cytotoxic in theirmechanism of action. However, stabledisease is not regarded as evidenceof therapeutic efficacy byregulatory authorities. Furthermore, ifbased on radiologic measurements Continued on page 968.alone, this designation encompasses aheterogeneous population that includespatients who demonstrate unequivocaltumor shrinkage as well asmany with tumor growth. Therefore,the case is presented to define stabledisease in terms of clinical benefit byincorporating alternative trial endpoints such as symptom control, QOL,or biologic end points.

The cytostatic, molecular-targeted therapies becoming available forlung cancer and other human solid tumors are more likely to result instable disease than to produce tumor regression. In the setting ofadvanced lung cancer, stable disease provides significant benefit to thepatient. However, in the context of clinical trials, stable disease isvaguely defined, difficult to measure, and may represent a heterogeneouspatient population. The inclusion of alternative trial end pointssuch as symptom improvement and biologic activity may help to identifypatients who have achieved clinically relevant stable disease. Theepidermal growth factor receptor–tyrosine kinase inhibitor gefitinib(Iressa) has been shown to produce partial responses and stable diseasein patients with advanced lung cancer who have previously receivedtreatment with standard chemotherapies. In the monotherapy trials ofgefitinib, stable disease was correlated with improvements in diseaserelatedsymptoms and quality of life-the most meaningful end pointsfor the patient with advanced lung cancer. Thus, with the introductionof new molecular-targeted agents, stable disease with clinical benefitshould become an important goal of anticancer therapy.

In a campaign mounted against theuse of prophylactic cranial irradiation(PCI) in small-cell lung cancer(SCLC), the battle cry of the anti-PCI crowd 10 to 15 years ago was“Fry now, pay later.” The problemwas that some patients survived andseemed to suffer from the treatment.In those days, the high frequency ofbrain metastasis was underestimated.It was commonly thought that withoutPCI, 20% of patients failed at sitesin the brain, and with PCI, only 5%failed.

Prophylactic cranial irradiation(PCI) in patients with locallyadvanced non–small-cell lungcancer (NSCLC) remains an area ofcontroversy. Dr. Gore has provided areview of the literature, including randomizedand nonrandomized studiesand, in particular, the ongoing RadiationTherapy Oncology Group trial(RTOG 0214), which is randomizingNSCLC patients to PCI or observation.

ROCKVILLE, Maryland—The Food and Drug Administration (FDA) has granted accelerated approval to Iressa tablets (gefitinib, AstraZeneca) as monotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) in patients whose disease has progressed despite treatment with platinum-based and docetaxel (Taxotere) chemotherapy. The Oncologic Drugs Advisory Committee (ODAC) had recommended approval of Iressa on September 24, 2002. However, the FDA delayed action on the recommendation for 3 months to analyze new Japanese data that indicated Iressa was associated with an unexpected and often-fatal rate of interstitial lung disease (ILD).

This review by Dr. Gore emphasizesthe significance of theproblem of brain metastases inpatients with locally advanced non–small-cell lung cancer (NSCLC). Thearticle should prompt medical and radiationoncologists to consider enrollingpatients in the ambitious study ofprophylactic cranial irradiation (PCI)led by the Radiation Therapy OncologyGroup (RTOG L-0214). Statisticsfrom the ongoing RTOG study arecomplicated, but essentially, the researchersare looking for a 20% increasein median survival for patientsreceiving PCI. This would make theimpact of PCI in NSCLC comparableto that observed in limited small-celllung cancer (SCLC).