NSCLC

Belinostat is currently in a Phase I/II trial in combination with paclitaxel plus carboplatin in chemotherapy naive patients with Stage IV NSCLC.

Disease Overview
Lung cancer is the leading cause of cancer-related mortality in the United States. Approx 222,520 new patients are diagnosed with lung cancer every year in the US with more than 157,300 deaths from the disease. The 5-year relative survival rate for the period of 1995 to 2001 for patients with lung cancer was 15.7%.
Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies. The most common histologies are adenocarcinoma, squamous carcinoma and large cell carcinoma.

Risk Factors
Risk factors that contribute to the development of lung cancer include:

Cigarette, pipe, or cigar smoking.
Exposure to second-hand smoke, radon, arsenic, asbestos, chromates, chloromethyl ethers, nickel, polycyclic aromatic hydrocarbons, radon progeny, other agents, and air pollution.
Radiation therapy to the breast or chest.

The single most important risk factor for the development of lung cancer is smoking. For smokers, the risk for lung cancer is on average tenfold higher than in lifetime nonsmokers (defined as a person who has smoked <100 cigarettes in their lifetime). The risk increases with the quantity of cigarettes, duration of smoking, and starting age. Smoking cessation results in a decrease in precancerous lesions and a reduction in the risk of developing lung cancer. Former smokers continue to have an elevated risk for lung cancer for years after quitting. Asbestos exposure may exert a synergistic effect of cigarette smoking on the lung cancer risk.

Diagnosis and Treatment

At diagnosis, patients with NSCLC can be divided into three groups that reflect both the extent of the disease and the treatment approach.

Surgically resectable disease
The first group of patients has tumors that are surgically resectable (generally stage I, stage II, and selected stage III tumors). This group has the best prognosis, which depends on a variety of tumor and host factors. Patients with resectable disease who have medical contraindications to surgery are candidates for curative radiation therapy.

Locally and/or regionally advanced disease
The second group includes patients with either locally (T3-T4) and/or regionally (N2-N3) advanced lung cancer. Selected patients with locally advanced tumors may benefit from combined modality treatments. Patients with unresectable or N2-N3 disease are treated with radiation therapy in combination with chemotherapy. Selected patients with T3 or N2 disease can be treated effectively with surgical resection and either preoperative or postoperative chemotherapy or chemoradiation therapy.

Distant metastatic disease
The final group includes patients with distant metastases (M1) that were found at the time of diagnosis. This group can be treated with radiation therapy or chemotherapy for palliation of symptoms from the primary tumor. Patients with good performance status (PS), women, and patients with distant metastases confined to a single site live longer than others.

The Web site of the National Cancer Institute (http://www.cancer.gov)