Therapy of Non-Small Cell Lung Cancer: Past, Present, and Future

Steven A. Sandler, MD
Published: Monday, Apr 09, 2012

Abstract

For years, the progress in treating non–small-cell lung cancer (NSCLC) had reached a plateau. In the last decade, primarily because of molecular oncology, translational research has emerged as the foundation for new therapies for this resistant disease. Recently, we have seen a paradigm shift in our approach to NSCLC. New and relevant studies are examining the role of histology, biomarkers, and growth factor receptor inhibitors in the treatment of NSCLC. The expanding role of identifying “driver mutations” will lead to more effective therapies. This review explores some of the emerging options for the treatment of NSCLC.

The National Cancer Institute estimated that 222,520 individuals (116,750 men and 105,770 women) were diagnosed with and 157,300 individuals (86,200 men and 71,000 women) died of cancer of the lung and bronchus in 2010.1 The cure rate for this disease is estimated to be only 15%.

Prevention

Results of 2 major trials should help us to better define our screening strategies. Previous lung cancer screening trials showed that screening did not decrease mortality. However, several shortcomings in these trials may have failed to detect a small screening benefit.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial began in November 1993 and ended in July 2001. This was a randomized controlled study that included 154,901 participants aged 55-74 years and was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers. Participants received a baseline chest radiograph (CXR), followed by 3 annual single-view CXRs at the 10 US screening centers versus a usual-care control group. The results showed that lung cancer mortality was not reduced when annual CXR screening was compared with usual care in high-risk individuals.2

From August 2002 through April 2004, the National Lung Screening Trial enrolled 53,454 persons at high risk for lung cancer at 33 medical centers in the United States.3 Eligible participants were between 55 and 74 years of age at the time of randomization, had a history of cigarette smoking of at least 30 pack years, and, if former smokers, had quit within the previous 15 years. Persons who had previously received a diagnosis of lung cancer, had undergone chest computed tomography (CT) within 18 months before enrollment, had hemoptysis, or had an unexplained weight loss of more than 6.8 kg (15 lb) in the preceding year were excluded. Participants were randomly assigned to undergo 3 annual screenings with either low-dose CT or single-view postero/anterior chest radiography. The study demonstrated a 20% reduction in lung cancer deaths with low-dose helical CT screening in high-risk patients compared with a conventional CXR.3

Adjuvant Therapy

Surgery is the primary treatment modality for patients with early-stage operable NSCLC. Approximately half of these patients eventually experience relapse after resection, with a much higher proportion of distant metastases than local recurrences. The 5-year survival rates for NSCLC range from 45% to 50% in stage I, 30% to 35% in stage II, 15% in stage IIIA, 5% in stage IIIB, and only 1% in stage IV.4

The International Adjuvant Lung Cancer Trial, the largest cisplatin-based adjuvant study, showed positive results after a median follow-up of 56 months, but the significant effect was no longer present after a median follow-up of 90 months.5 The lack of long-term survival may be because of the toxicity of chemotherapy or other comorbidities. In the recently updated Medical Research Council meta-analysis and in the Lung Adjuvant Cisplatin Evaluation, the 5-year absolute benefit of chemotherapy compared with placebo ranged from 4% to 5.3% (P < .0000001 and P = .004, respectively).6,7 The most common chemotherapy regimen in the trials and the most robust data for adjuvant chemotherapy outside the United States are with the use of vinorelbine (Navelbine) and cisplatin. This regimen does not enjoy such popularity in the United States.


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