Lung Cancer

Erlotinib (Tarceva) is an orally available selective small-moleculeinhibitor of HER1/EGFR tyrosine kinase with a 50% inhibitory concentrationof 2 nM for purified tyrosine kinase. This agent has beenshown to produce stasis or regression of tumor growth in human cancerxenograft models, including non-small-cell lung cancer models.Ongoing preclinical investigations indicate that inhibition of the MAPKand Atk signaling pathways downstream of HER1/EGFR may be requiredfor optimal antitumor effects. Erlotinib exhibits inhibition ofMAPK and Atk kinases at concentrations higher than those requiredfor HER1/EGFR tyrosine kinase inhibition; such findings suggest thatmaximal inhibition of HER1/EGFR, requiring high erlotinib doses, isnecessary for optimum antitumor activity. These considerations aresupported by tumor models, including non-small-cell lung cancermodels, showing dose-related antitumor effects up to high doses oferlotinib. Erlotinib exhibits additive antitumor effects when combinedwith chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel,gemcitabine [Gemzar], and capecitabine [Xeloda]), radiation therapy,and other targeted agents (eg, bevacizumab [Avastin]). Recent studiesindicate that erlotinib inhibits the EGFRvIII mutant at concentrationshigher than those required for inhibition of wild-type receptor. Ongoinginvestigation will help to determine optimal dosing and dose frequencyof erlotinib in various cancers in the clinical setting.

Non–small-cell lung cancer represents a growing global burden andremains a therapeutic challenge. Only small improvements in survivalhave been made with standard chemotherapeutic approaches to advanceddisease in recent history. Novel biologic targeted therapies offerthe potential of improving patient management and treatment outcomesin non–small-cell lung cancer. Prominent among these novelagents are the HER1/epithelial growth factor receptor (EGFR) inhibitors.One of these agents, gefitinib (Iressa), is already approved for usein advanced, refractory non–small-cell lung cancer. Erlotinib (Tarceva)is a promising HER1/EGFR inhibitor in phase III evaluation as firstlinetherapy combined with chemotherapy and as second-/third-linemonotherapy in advanced non–small-cell lung cancer. In addition,erlotinib is being evaluated in combination with the angiogenesis inhibitorbevacizumab (Avastin), a strategy combining two new modalitiesin cancer treatment. Results of these trials will provide importantinformation on optimal use of these new targeted therapies and mayoffer the promise of improving the treatment of non–small-cell lungcancer.

In phase I trials in healthy volunteers and patients with refractorycancers, erlotinib (Tarceva) was well tolerated and showed activityagainst non–small-cell lung cancer and other tumors. The dose identifiedfor further clinical development was 150 mg/d; at this dose, erlotinibachieves high exposure, with maximum concentrations greater than2,000 ng/mL and 24-hour area under the concentration-time curvegreater than 35,000 ng • h/L. In a phase II trial in 57 patients withpreviously treated advanced non–small-cell lung cancer, erlotinib treatmentproduced an objective response rate of 12.3% and a stable diseaserate of 38.6%, with median duration of response of 19.6 weeks;median overall survival was 8.4 months and 1-year survival was 40%,with 9 patients remaining alive over follow-up of greater than 18 months.No grade 4 toxicity was observed, and grade 3 toxicity was minimal. Inan ongoing phase II trial in bronchioloalveolar carcinoma, erlotinibtreatment has produced objective response in 26% of 50 evaluable patients,with median duration of response not yet having been reached.An ongoing phase II trial is examining the combination of erlotinibwith the angiogenesis inhibitor bevacizumab (Avastin) in previouslytreated non–small-cell lung cancer; phase I evaluation revealed no doselimitingtoxicities at tested doses and provided evidence of antitumoractivity. Two phase III trials are examining erlotinib in combinationwith carboplatin (Paraplatin)/paclitaxel (the TRIBUTE trial) orcisplatin/gemcitabine (Gemzar) (the TALENT trial) as first-line treatmentin advanced non–small-cell lung cancer. The phase III BR.21trial is assessing erlotinib monotherapy in advanced refractory non–small-cell lung cancer. Results of these phase II trials will soon beavailable.

The identification of predictive or surrogate markers of response toHER1/epidermal growth factor receptor (EGFR) inhibitor treatmentwould permit selection of patients most likely to respond to such treatment.Markers could consist of tumor characteristics (eg, characteristicsof the receptor or downstream signaling molecules and determinantsof resistance) or host characteristics (eg, pharmacokinetic parametersand toxicities). The occurrence of rash may constitute a surrogatemarker of response to erlotinib (Tarceva) treatment in patientswith non–small-cell lung cancer and other cancers. The erlotinib markeridentification program has been designed to identify and investigateother candidate markers by analysis of a large number of clinicalsamples from patients enrolled in erlotinib trials in non–small-cell lungcancer, including the phase III TALENT and TRIBUTE trials oferlotinib combined with chemotherapy and the phase III BR.21 trial oferlotinib monotherapy in advanced non–small-cell lung cancer. Thisprogram should both contribute to understanding of the molecular biologyof HER1/EGFR inhibition and result in identification of potentialmarkers that can be evaluated in the clinical setting.

Moderate consumption of red wine may decrease the risk of lung cancer in men, according to a study published in the October Cancer Epidemiology, Biomarkers and Prevention journal (17: 2692–2699, 2008).

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.

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.

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."