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New Studies in Lung Cancer Prevention and Detection Reveal Positive Results

It was a big week in lung cancer with the International Association for the Study of Lung Cancer (IASLC) meeting and two new studies on lung cancer prevention and detection that caught the attention of oncologists this week. One study focused on reducing the incidence of the disease in high-risk individuals, while the other study sought to detect tumors at early stages.

Lung Cancer Prevention with Celecoxib in Former Smokers

Celecoxib [Celebrex; Pfizer] continues to show a favorable response in bronchial Ki-67 expression suggesting its efficacy for lung cancer chemoprevention. Results from a study conducted by Jenny T. Mao, MD, of the New Mexico VA Health Care System/University of New Mexico and colleagues are published in this month’s July issue of Cancer Prevention Research.

“Former smokers with high baseline Ki-67 labeling index likely have a stronger driving force of cancerization in their lungs,” said Dr. Mao in an interview. The bronchial Ki-67 labeling index after 6 months of treatment was the primary endpoint as Ki-67 expression is a marker of cellular proliferation.

The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway is known to play a pivotal role in carcinogenesis, thus inhibiting COX-2 may help to prevent lung cancer.

The 137 participants in this phase 2b, randomized, double-blind, placebo-controlled study were former smokers who had smoked at least 30 pack-years; quit and abstained from smoking for at least 1 year; had no evidence of major cardiovascular, renal, or hepatic abnormalities; and successfully completed bronchoscopy without evidence of cancer or other important findings. Participants were randomized in a 1:1 ratio to receive 6 months of celecoxib (400 mg orally twice each day) or placebo.

Celecoxib decreased the bronchial Ki-67 labeling index by an average of 34% after 6 months of treatment, while placebo increased the Ki-67 labeling index by 3.8%.

Celecoxib was associated with reduced or resolved CT-detected lung nodules. “Oral celecoxib is biologically active in both the central and peripheral respiratory epithelium. This is the first time the improvement of a central bronchial biomarker in response to a lung cancer chemopreventive agent has been linked to the favorable modulation of potential precursor lesions in the lungs,” said Dr. Mao.

Responders to celecoxib could be predicted by their baseline COX-2/15-PGDH ratio, which was 2.9-fold higher than the ratio in nonresponders. Dr. Mao stated, “This is the first study to demonstrate that the expression of key enzymes for a molecular target may help predict an individual's responsiveness to a lung chemopreventive agent. These findings will help guide the development of a more focused, personalized approach and improve the selection of individuals that will more likely benefit in future lung cancer chemoprevention trials with celecoxib.”

This study was supported by the National Cancer Institute, and Pfizer Inc. supported study drugs and plasma celecoxib measurements.

Low-Dose CT Screening Reduces Lung Cancer Mortality

According to research published June 29 in the New England Journal of Medicine by the National Lung Screening Trial Research Team, mortality from lung cancer showed a 20% relative reduction when screening with low-dose helical computed tomography was compared with screening by chest radiography.

The 53,454 study participants were between the ages of 55 and 74 years old, had a cigarette smoking history of at least 30 pack-years, and, if they had quit smoking, they had done so within the last 15 years. Participants were randomized to be screened by low-dose CT or by single-view posteroanterior chest radiography, and then were screened 3 times at 1-year follow-up intervals.

Mortality rates in the low-dose CT group due to lung cancer showed 247 deaths per 100,000 participants compared with 309 deaths per 100,000 in the radiography group.

“The findings show that CT screening reduces lung cancer mortality by 20 percent when compared with chest x-ray, giving physicians and patients better information than before on which to base their conversations about lung cancer screening. This study was very well designed in order to eliminate many of the weaknesses that affected other such studies,” explained Albert Rizzo, MD, American Lung Association Board Chair-Elect and a pulmonary and critical care physician.

The rate of positive tests in all 3 rounds of screening was higher in the low-dose CT group, with 39% of the low-dose CT group and 16% of the radiography group having at least one positive screening result. The positive results were false positives for 96.4% of those in the low-dose CT group and 94.5% of those in the radiography group.

“Questions remain about the cost effectiveness of screening, the amount of over-diagnosis in the study, whether populations with different risk profiles benefit from screening and how the results will translate to community settings,” said Dr. Rizzo. He stated that more research is needed to see the benefit in the community.

This trial was funded by the National Cancer Institute.

by Kathy Boltz, PhD

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