Fadlo R. Khuri, MD | Authors



Lung Cancer in the Elderly: What’s Age Got to Do With It?

November 15, 2010

The review by Dr. Chiappori and colleagues in this issue of ONCOLOGY addresses an important challenge relating to the optimal management of elderly patients with lung cancer. The authors provide an excellent overview of the data in patients with various stages of non-small cell lung cancer (NSCLC). They also highlight the limitations of the existing data in the management of elderly NSCLC patients.

Through the Looking Glass: The Evolution of Erythropoiesis-Stimulating Agent Use

March 22, 2010

The perception and reality of the clinical value of erythropoiesis-stimulating agents (ESAs) in cancer supportive care have undergone a dramatic transformation since their initial use in 1990. The perception of ESA value in patients has evolved from panacea to miscreant over a 2-decade period of laboratory research, clinical trial data, and postmarketing experience. Meanwhile, the real clinical benefits of ESAs have changed very little from those described in the joint American Society of Clinical Oncology/American Society of Hematology guidelines originally published in 2002.[1] Even then, the value of initiation of ESAs was clear only in patients with hemoglobin values < 10 g/dL; quality-of-life measures produced inconsistent and, therefore, clinically inapplicable, results; and ESA use was shown to reduce the proportion of patients requiring red blood cell (RBC) transfusions by approximately 20%. The reality of ESA use that came to light following approval was increased mortality rates in certain populations, higher tumor progression and cancer recurrence rates, and more frequent and severe serious adverse effects including thromboembolism, stroke, and cardiovascular events.

Cancer Management Chapter 3: Non–small-cell lung cancer

March 08, 2010

Lung cancer has been the leading cause of cancer death among men in the United States for years, and since 1988, it has become the number-one cause of cancer death among women. An estimated 219,440 new cases of lung cancer are expected in 2009, and 159,390 deaths due to this disease are expected to occur, roughly 30% of all cancer deaths. This exceeds the combined number of deaths from the leading causes of cancer (breast, prostate, and colon cancers). It accounts for 6% of all deaths in the United States.

Preoperative Therapy for Early-Stage NSCLC: Opportunities and Challenges

September 14, 2009

The treatment of early-stage non–small-cell lung cancer (NSCLC) has undergone a paradigm shift recently with the addition of systemic therapy to local therapy. The use of cisplatin-based chemotherapy following surgery is now a standard approach for patients with stage II–IIIA disease.

State of the Art in Lung Cancer: A Glass One-Quarter Full?

February 01, 2007

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.

Targeting the Epidermal Growth Factor Receptor

February 01, 2006

The epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.

Induction Chemotherapy for Resectable Non–Small-Cell Lung Cancer

November 01, 2004

Recent advances in molecularclassification and the adventof noncytotoxic molecularlytargeted therapies have offered increasedhope of improving the diagnosis,treatment, and prognosis forpatients with non–small-cell lung cancer(NSCLC).[1] Yet the use of chemotherapyin NSCLC has continuedto evolve over recent years with theappearance of newer cytotoxic agentsthat have improved the outcome forpatients. Doublet combination chemotherapyhas become the standardof care for patients with advanceddisease and good performance status.Prolongation of survival has also beenshown with second-line chemotherapyfor patients whose tumors are refractoryto first-line agents.[1]

Commentary (Cohen/Khuri): Treatment of Non–Small-Cell Lung Cancer in Older Persons

January 01, 2003

The importance of cancer as aproblem in the elderly is gainingincreasing appreciationdue, in part, to the demographicchanges taking place in this countryand around the world and their associationto the incidence of cancer.Ongoing epidemiologic research overthe past several decades has consistentlyconfirmed the continuing trendtoward an aging population. In theUnited States, an anticipated 20.1%of the population will be 65 years ofage or older by 2030, the number ofpeople 75 years of age or older willhave tripled, and the 85-or-older agegroup will have doubled.[1]

Commentary (Khuri/Smythe): Diffuse Malignant Mesothelioma of the Pleural Space and Its Management

July 01, 2002

Malignant pleural mesothelioma is a relatively rare malignancy with an annual incidence in the United States of approximately 3,000 cases. Based on asbestos exposure demographics, incidence should peak in the United States in the next 10 to 20 years. Peto et al have suggested that the incidence in Western Europe may continue to climb for substantially longer, possibly reaching as high as 1/100 among middle-aged men.[1,2] In developing countries (often bereft of asbestos regulation), the incidence is not known