Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective.

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small-cell lung cancers (NSCLCs). This presents an opportune target for new treatment strategies designed to selectively interfere with the cancer cell growth cycle. Recent investigations into the biology of the EGFR and its downstream signaling pathways have reminded us of the complexity of cancer cell communications from the cytoplasm to the nucleus.

Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.

Purpose: To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.

Patients And Methods: Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m(2) intravenously (i.

Chemoprevention of lung cancer--from biology to clinical reality.

Lung cancer is the commonest cause of cancer death in developed countries and throughout the world. Cigarette smoking is the main risk factor for lung cancer and ex-smokers today comprise approximately 50% of all new lung cancer cases. Chemoprevention builds on the concepts of field of cancerization and multistep carcinogenesis and can be defined as the use of natural or chemical compounds to prevent, inhibit or reverse the process of carcinogenesis.

Combinations of three chemotherapeutic agents and two chemotherapeutic agents plus a targeted biologic agent in the treatment of advanced non small-cell lung cancer.

Lung cancer is the most common cause of cancer death in the world. In the United States, more than 28% of all cancer deaths are from lung cancer. In the past decade, a number of new drugs were introduced into the treatment of lung cancer including taxanes, gemcitabine, vinorelbine, and irinotecan.

Irinotecan and platinums in the treatment of non small-cell lung cancer.

Lung cancer is the leading cause of cancer death in the United States and in the world. In the United States, lung cancer ranks first in cancer deaths for both men and women. The 5-year survival rate is only 15%, but this has improved considerably from the 5% rate in the early 1960s.

Targeting the epidermal growth factor receptor in non-small cell lung cancer.

Fifteen% or fewer of patients with non-small cell lung cancer (NSCLC) survive 5 years. The current standard of care for patients with locally advanced or metastatic NSCLC is systemic chemotherapy with a two-drug combination regimen that includes a platinum agent. Although systemic chemotherapy reduces the rate of death attributable to lung cancer, disease progression is inevitable and dose-limiting toxicities restrict their use.

The future of cyclooxygenase-2 inhibitors and other inhibitors of the eicosanoid signal pathway in the prevention and therapy of lung cancer.

Recent advances in the understanding of the biology and molecular biology of lung cancer has provided targets for novel therapeutic and chemoprevention strategies. The eicosanoid/prostaglandin signal pathway is involved in the metabolism of membrane phospholipids to end products that are involved in apoptosis, proliferation, differentiation, and angiogenesis. Abnormalities in this pathway occur frequently in lung cancer, including the overexpression of cytoplasmic phospholipase A2, cyclooxygenase-2 (COX-2), prostaglandin E (PGE) synthase, PGE2, 5-lipoxygenase (LOX), 8-LOX, and 12-LOX.

The role of irinotecan combined with Cisplatin or Carboplatin in the treatment of advanced non-small-cell lung cancer.

More than one third of all non-small-cell lung cancer (NSCLC) patients present with advanced stage IV disease with metastases or with stage IIIB disease with a malignant pleural or pericardial effusion. The prognosis for these patients remains poor despite some improvement in survival produced by 2-drug chemotherapy combinations. With the best 2-drug combinations, the expected median survival is 8-9 months and > 80% of patients die within 2 years of diagnosis.

Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction.

Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of > or = 30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing.

Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.

Purpose: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood.

Materials And Methods: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies.

Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study.

Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30) were anesthetized with a 25% pentobarbital solution and received a cuff around the right sciatic nerve.

Ongoing and future trials of biologic therapies in lung cancer.

Lung cancer is the leading world-wide cause of cancer death. The care rate remains less than 15% despite improvements in surgery, radiotherapy and chemotherapy. The majority of deaths can be attributed to systemic metastases.

Understanding the mechanisms of action of EGFR inhibitors in NSCLC: what we know and what we do not know.

The development of rationally designed agents targeting specific biological pathways in tumor development has been heralded as a major paradigm shift in the approach to the treatment of cancer. The application of these agents has lead to promising pre-clinical findings in a variety of human cancer pre-clinical models including lung cancer. Results from initial clinical trials employing targeted agents have shown that in contrast to what was expected, only selected patients may benefit.

Exisulind-induced apoptosis in a non-small cell lung cancer orthotopic lung tumor model augments docetaxel treatment and contributes to increased survival.

We reported previously a significant increase in survival of nude rats harboring orthotopic A549 human non-small cell lung cancer tumors after treatment with a combination of exisulind (Sulindac Sulfone) and docetaxel (D. C. Chan, Clin.

Taxanes in the treatment of advanced (stage III and IV) non-small cell lung cancer (NSCLC): recent developments.

Taxanes, paclitaxel, and docetaxel have become the cornerstone of both first-line and second-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Recently, several pivotal phase III randomized trials have been published. These studies and phase II trials will be discussed.

Pemetrexed safety and dosing strategy.

Pemetrexed is a novel antifolate/antimetabolite that inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide transformylase. As a class, antifolates have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities carries a high risk of potentially life-threatening complications.

Bradykinin antagonists as new drugs for prostate cancer.

Bradykinin (BK) is an autocrine growth factor for lung and prostate cancers. BK also facilitates tumor extension by increasing tissue permeability and stimulating angiogenesis. Peptide BK antagonists are in development as potential new drugs for lung cancer.

Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small cell lung cancer.

The majority of non-small cell lung cancers (NSCLCs) overexpress the epidermal growth factor receptor (EGFR). The EGFR is frequently overexpressed in preneoplastic bronchial lesions. Thus, EGFR is an excellent potential target for prevention and therapy.