Frontiers in Clinical Drug Research - Anti-Cancer Agents: Volume 1

Atta-ur-Rahman

• Publisher: Bentham Science Publishers
• ISBN:
  9781608057986
• Topic: Physical Sciences
• Subtopic: Clinical Chemistry

Frontiers in Clinical Drug Research - Anti-Cancer Agents - Volume 1 should prove to be a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field. The chapters in this volume have been written by leading experts from the field.
The contents of this book include new approaches to cancer therapy, treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors, targeting key signaling pathways in pediatric brain tumors, current status of cladribine in lymphoid and myeloid malignancies, natural anti-cancer products and the mechanisms of telomere and telomerase regulation in hematologic malignancies.
The eBook series is essential to all scientists involved in clinical drug research who wish to keep abreast of rapid and important developments in the field. The readers will find these reviews valuable and will certainly trigger further research in the pharmaceutical development of anti-cancer agents.

The Treatment of Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Vera Hirsh^*

Chief, Hematology-Oncology Services, Santa Cabrini Hospital; Associate Physician, Oncology Services, Royal Victoria Hospital and Montréal General Hospital; Associate Professor, Department of Oncology, Faculty of Medicine, McGill University, Montréal, Québec, Canada

Abstract

Lung cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer-related mortality in North America. The heterogeneity of non-small cell lung cancer (NSCLC) and the importance of linking new, targeted agents to the appropriate disease subtype require an individualized approach to treatment. In patients with epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (EGFR-TKIs) provide a highly effective treatment option, with improved toxicity compared with standard chemotherapy. Newer irreversible EGFR-TKIs have additional advantages and are able to overcome the resistance seen with the older reversible agents. A number of clinical trials using EGFR-TKIs are showing promising results, including a superior side-effect profile and improved quality of life when compared with standard chemotherapy. Studies using EGFR-TKIs will aid in determining the optimal positioning of these therapies. With improvements in both testing and access to treatment, targeted use of EGFR-TKIs may greatly improve outcomes in NSCLC.

Keywords:: Non-small cell lung cancer, epidermal growth factor receptor, epidermal growth factor receptor mutation, epidermal growth factor receptor-tyrosine kinase inhibitors, afatinib, erlotinib, gefitinib, adverse drug event, skin rash, diarrhea, quality of life.

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^* Corresponding author Vera Hirsh: Chief, Hematology-Oncology Services, Santa Cabrini Hospital; Associate Physician, Oncology Services, Royal Victoria Hospital and Montréal General Hospital; Associate Professor, Department of Oncology, Faculty of Medicine, McGill University, Montréal, Québec, Canada;, E-mail: [email protected]

EPIDEMIOLOGY OF LUNG CANCER

Lung cancer is the leading cause of cancer-related mortality in the United States. Each year, for the past 25 years, more women have died from lung cancer than

breast cancer. The estimated number of new cases of lung cancer in 2012 is 226,160, approximately 14% of all cancer diagnoses for the year. The number of deaths due to lung cancer is estimated at 160,340. The five-year survival rate for all lung cancers is 16%, higher (52%) if diagnosed at an early stage. However, only 15% of cases present when the disease is localized as the majority of patients present with advanced stage disease at diagnosis [1, 2].

The biggest risk factor for lung cancer is cigarette smoking, causing up to 90% of cases in the United States [3]. Risk increases with the duration of smoking and the number of cigarettes smoked. Risk of lung cancer also increases with pipe and cigar smoking. Second-hand smoke, smoke inhaled from other people’s cigarettes, pipes, and cigars, causes approximately 3,000 lung cancer deaths in people who have never smoked [3]. The second leading cause of lung cancer in North America is exposure to radon gas, which is emitted from rocks, soil, and building materials, accounting for 20,000 new cases of lung cancer each year in the United States [3]. Other risk factors include exposure to toxic substances such as asbestos, arsenic, cadmium, and chromium, and a family history of lung cancer [2].

Lung cancer is classified by histology type. The majority of lung cancers come from malignancies of the epithelial cells, or carcinomas, with the two main types being small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC makes up approximately 85% of all lung cancers [2].

NON-SMALL CELL LUNG CANCER

NSCLC consists of a heterogeneous group of histologies traditionally grouped together because of similarities in treatment and prognosis. The three main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, with other types occurring less frequently [4, 5].

Adenocarcinoma — the most common type of NSCLC — comprises 40% of all lung cancers. It usually originates in the periphery of the lung and is slow growing, taking years to become invasive. This type of lung cancer occurs primarily in smokers. However, it is also the most common type of lung cancer in never smokers [6]. Adenocarcinoma is more common among Asian populations [7] as well as women [6, 8].

Squamous cell carcinoma accounts for between 25% and 30% of lung cancers. It usually originates centrally in the larger bronchi and, like adenocarcinoma, is slow growing [6, 9]. This type of lung cancer is almost always linked to smoking.

Large-cell carcinoma makes u...