ONCOLOGY Vol 16 No 9

Edited by John Mendolsohn, MD, Peter M. Howley, MD, Mark A. Israel, MD, and Lance A. Liotta, MD, PhD, The Molecular Basis of Cancer is designed for students, researchers, and physicians in a variety of disciplines. It does not provide a detailed description of the clinical manifestations of human neoplasia. There is, instead, an extensive presentation of the scientific basis of cancer development and therapy. The book includes the contributions of 61 authors, virtually all of whom are recognized experts in their respective fields, from throughout the United States and Europe. The references are comprehensive and relatively current, given the lag time in going to press. The book will certainly benefit both basic scientists and clinicians alike.

Since our first "Quality of Life in Current Oncology Practice and Research" symposium was held at St. Mary Medical Center in Long Beach, California in February 1989, and published in ONCOLOGY in May 1990, there has been a marked increase in the use of quality of life measures to determine the outcomes of interventions in clinical oncology. Measuring the effects of anemia treatment with quality of life tools is a fine example of the importance of these tools to gauge the impact and clinical significance of interventions. It is, therefore, both timely and relevant that we dedicate our fifth symposium to the management of anemia in patients with cancer.

On the following pages are examples of commonly used scales for evaluating quality of life and symptoms associated with anemia in patients with cancer. Please note that some of the scales are copyrighted (and marked as such herein) and may not be reproduced in anyway without the express written consent of the copyright holders.

The anemia of chronic disease traditionally is defined as a hypoproliferative anemia of no apparent cause that occurs in association with an inflammatory, infectious, or neoplastic disorder, and resolves when the underlying disorder is corrected. Disordered iron metabolism as manifested by a low serum iron, decreased serum transferrin, decreased transferrin saturation, increased serum ferritin, increased reticuloendothelial iron stores, increased erythrocyte-free protoporphyrin, and reduced iron absorption, is a characteristic feature of the anemia of chronic disease and has been thought to be a major factor contributing to the syndrome.

The bone marrow failure states, aplastic anemia and myelodysplastic syndrome, are characterized by reticulocytopenic anemia, with variable neutropenia and thrombocytopenia. The bone marrow biopsy is very hypocellular in aplastic anemia, but it is usually hypercellular in myelodysplastic syndrome.

To support evidence-based clinical guidelines on erythropoietin use for anemia in oncology, we conducted systematic reviews of controlled trials on four patient groups. These were patients with treatment-related anemia; patients with disease-related anemia; patients transplanted with allogeneic hematopoietic stem cells; and those transplanted with autologous hematopoietic stem cells.

In its hormonal role, erythropoietin is produced by the kidney in response to hypoxic stress and signals the bone marrow to increase the number of circulating erythrocytes. It has become clear in recent years, however, that erythropoietin and its receptor are members of a cytokine superfamily that mediates diverse functions in nonhematopoietic tissues. Nonhormonal erythropoietin actions include a critical role in the development, maintenance, protection, and repair of the central nervous system (CNS).

This article examines the relationships between chemotherapy-induced anemia, fatigue, and psychological distress among anemic cancer patients with solid tumors.

The clinical development of recombinant human erythropoietin (rHuEPO) has had a remarkable impact on the clinical practice of oncology. A decade ago, randomized, placebo-controlled trials in anemic cancer patients demonstrated that rHuEPO resulted in an improvement in hemoglobin and hematocrit, a reduction in transfusion requirements, and improvement in quality-of-life (QOL) end points. Based on these trials, recombinant erythropoietin was approved for the treatment of anemia in patients with nonmyeloid malignancies in whom the anemia was caused by the effect of chemotherapy.

Symptom burden is certainly not a new concept in the literature on disease and treatment, but recent developments in our understanding of how to measure symptoms and their impact make it possible to cast symptom burden as a reasonable summary measure of both disease- and treatment-outcome status. We discuss the use of symptom burden as an alternative to quality-of-life measures or as a supplement to these measures.

Barriers to use of erythropoietic therapy in cancer patients include nonresponse in a sizable proportion, resultant lowering of cost-effectiveness, and inconvenience. Darbepoetin alfa represents the outcome of efforts to develop agents with improved erythropoietic potency.

Fatigue is common in patients with cancer. Fatigue is very distressing to patients, who often view it as an indication that their disease is progressing or that treatment is ineffective.

One of the most fundamental challenges to multicellular life is the delivery of sufficient oxygen and metabolic substrate to all cells and the rapid elimination of acid formed during cellular respiration. Thus it is logical to wonder whether anemia, by compromising these pathways, might contribute to the progression of cancer.

The term "blood substitute" is commonly misused when "red cell substitute" is meant. The ideal red cell substitute should deliver oxygen (O2), require no compatibility testing, cause few side effects, have prolonged storage qualities, persist in the circulation, and be available at reasonable cost. While no drug with all of these qualities is on the near horizon, several early generation red cell substitutes are approaching submission for licensure, at least for limited indications.

Anemia in cancer patients is associated with a decline in energy levels, activity levels, and quality of life, and these variables improve when hemoglobin levels rise. Importantly, the impact of improved hemoglobin levels on response to chemotherapy, radiation therapy, and survival time is under study.

Erythropoietin is the primary physiological regulator of erythropoiesis, and it exerts its effect by binding to cell surface receptors. It has recently been shown that both erythropoietin and its receptor are found in the human cerebral cortex, and that, in vitro, the cytokine is synthesized by astrocytes and neurons, has neuroprotective activity, and is up-regulated following hypoxic stimuli. In animal models, exogenous recombinant human erythropoietin has been reported to be beneficial in treating experimental global and focal cerebral ischemia and reducing nervous system inflammation

There is a growing recognition in oncology of the importance of maintaining or improving patients’ quality of life (QOL) throughout the disease course. With this goal in mind, many clinical trials in oncology now seek to evaluate QOL end points.

Anemia is the most common hematologic abnormality seen in patients with cancer. Anemia is associated with debilitating symptoms and poorer health-related quality of life and may result in less than optimal disease/treatment outcomes.

Fatigue is an extraordinarily common consequence of cancer and its treatment. Fatigue can result in diminished cognitive and physical functional capacity and may be the result of multiple causes.

The hallmark of hemolysis is shortened red blood cell survival in the peripheral blood. Hemolysis results in anemia only when bone marrow cannot keep up with the rate of red cell destruction. Even though anemia is very commonly observed in most cancer patients, hemolytic anemias are rather rare.

Anemia, common in people with cancer, can be due to the disease itself or to the associated therapy. Fatigue, the most prevalent of all symptoms experienced by cancer patients, is the primary symptom of anemia. Caused by many factors, fatigue, regardless of etiology, has an adverse impact on health-related quality of life.

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

For more than 2 decades, combination chemotherapy has been the standard treatment for patients with small-cell lung cancer. Despite high initial response rates in both extensive- and limited-stage disease, long-term survival

Lung cancer is the leading cause of cancer-related death in the United States. There was rapid progress in the treatment of lung cancer during past decades, but local control and survival rates are still poor.

Although treatment of advanced non-small-cell lung cancer has been improved with the availability of such new agents as the taxanes, topoisomerase inhibitors, vinorelbine (Navelbine), and gemcitabine (Gemzar), platinum-

Lung cancer is the leading cause of cancer-related death in males and females in the United States. Most patients have advanced disease at diagnosis. Chemotherapy is the treatment of choice for patients with good performance

The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent for small-cell lung cancer that may complement other agents and treatment modalities. Combination

Sanofi-Synthelabo recently announced that its platinum-based drug oxaliplatin (Eloxatin) has been approved by the US Food and Drug Administration (FDA) for use in combination with infusional fluorouracil (5-FU)/leucovorin in advanced colorectal cancer patients whose disease has recurred or progressed after bolus 5-FU/leucovorin plus irinotecan (CPT-11, Camptosar) therapy. The FDA approval is based on the response rate and improved time to tumor progression observed in an ongoing trial. Data that demonstrate a clinical benefit, such as improvement in disease-related symptoms or an increase in survival are not yet available.

Depending on what the Senate does in September, there is a slight chance Congress could act on the Medicare Market Acquisition Drug Price Act (H.R. 5167). Introduced by Rep. Pete Stark (D-Calif) in July, the bill would change the way Medicare reimburses oncologists for the oncology drugs they purchase to administer to patients in the office. Even the American Society of Clinical Oncology (ASCO) agrees change in the reimbursement format is necessary. Nevertheless, Paul A. Bunn, Jr, MD, president of ASCO, says, "Under this bill, reductions in Medicare reimbursement would make it very difficult for many doctors to continue providing high-quality treatment to people with cancer."

Officials from the American Society for Therapeutic Radiology and Oncology (ASTRO) have announced that Ann Barrett, md, of the University of East Anglia in the United Kingdom, and John J. Curry, of the American College of Radiology, have