Treating Anemia Can Reverse Declines It Causes in Physical Function and May Improve Clinical Outcomes

LONG BEACH, California—Treating anemia can reverse the declines it causes in physical function and quality of life for cancer patients and may have an impact on outcomes of cancer therapy, reported Simon Tchekmedyian, MD. Statistics suggest that anemia and its effects are under-recognized and undertreated, he noted, but barriers to treatment may fall as new therapeutic agents prove to be more effective and can be administered more easily and less frequently.

Dr. Tchekmedyian serves as medical director, cancer care services, at St. Mary Medical Center and Pacific Shores Medical Group in Long Beach, California, and associate clinical professor of medicine, University of California School of Medicine in Los Angeles. He was also co-chair of the Fifth Quality of Life in Oncology Symposium.

Normal hemoglobin levels are currently defined as 12 to 16 g/dL in females and 14 to 18 g/dL in males, although there is some controversy about what should be considered normal. There is fairly good consensus that hemoglobin levels below the normal range but above 10 or 11 g/dL indicate grade 1 or mild anemia. The most severe anemia, grade 4, occurs at hemoglobin levels below 6.5 g/dL.

The malignancy itself or chemotherapy and other therapies can cause decreased erythropoietin production or reduced responsiveness of the bone marrow to erythropoietin. These are probably the most common causes of cancer-related anemia. Other causes include iron/B-12 deficiency, nutritional deficiencies and endocrinopathies, blood loss (particularly occult gastrointestinal blood loss), shortened red cell survival/hemolysis, infection, renal disease, and a variety of hematologic and inflammatory disorders.

Current Approaches

Current therapeutic approaches to cancer-related anemia include erythropoietic agents, iron, and vitamin B-12, as well as nutritional support. Blood transfusions are reserved for more symptomatic, severe cases of anemia. "Rituximab (Rituxan) has evolved recently as a very interesting and potentially very useful option for patients with immune-mediated hemolytic anemia," Dr. Tchekmedyian said. "Therapy of the underlying process, especially the malignancy but also occult gastrointestinal bleeding, infection, and sepsis all play important roles," he added.

In between the severe cases of anemia that need to be reversed quickly by transfusions, and mild cases where a watch and wait approach may be reasonable, are cases with clinical symptomatology and quality of life issues that affect the ability of the patient to function. "In those cases, erythropoietin therapy is very useful," Dr. Tchekmedyian said. It can also be combined with transfusions to manage more severe anemias.

"Transfusions are certainly not without risk," Dr. Tchekmedyian warned, "although the risk has diminished with recent technologies. These risks include infections, including HIV and hepatitis, delayed hemolytic reactions, and lung damage.’’

Many Could Benefit

Of the 1.25 million people in the United States presently receiving chemotherapy for cancer, about 800,000 are anemic with hemoglobin levels less than 12 g/dL and about 210,000 are currently receiving erythropoietin, Dr. Tchekmedyian estimated. Another 500,000 cancer patients not on treatment are anemic, but only 38,000 are receiving erythropoietin treatment.

Tumor types more commonly associated with cancer-related and chemotherapy-related anemia and treated with human recombinant erythropoietin (rHuEPO) are breast cancer, lung cancer, non-Hodgkin’s lymphoma, ovarian cancer, myeloma, and colon cancer (see Figure 1). Synchronizing chemotherapy and erythropoietin treatments can help make anemia treatment much more convenient, Dr. Tchekmedyian noted.

A study conducted among 169 cancer patients at Pacific Shores Medical Group found that 38% were anemic prior to chemotherapy and an additional 40% became anemic during chemotherapy. Overall, 63% of all cancer patients on chemotherapy received erythropoietin and only 6% of patients had blood transfusions.

Anemia Will Likely Increase

Most guidelines say erythropoietic therapy can be administered to patients with hemoglobin of less than 10 g/dL who are on chemotherapy, yet only one-third are benefiting from that therapy, Dr. Tchekmedyian reported. A survey of hematologists and oncologists revealed several factors (other than cost) that interfere with the administration or prescription of erythropoietic agents in chemotherapy-induced anemia. Factors listed include poor reimbursement, mode or inconvenience of administration for patients, the belief that not all patients require treatment, lack of efficacy in some patients, and limited and restricted indications. Newer therapeutic agents, such as darbepoetin alfa (Aranesp), offer increased efficacy and less frequent dosing and might help overcome these barriers.

Despite the perception that anemia should be treated only when hemoglobin dips below 10 g/dL, "quality of life data indicate that actually the larger incremental improvement occurs between hemoglobin levels of 10 and 12 or 13," Dr. Tchekmedyian said. Additional research may trigger treatment of patients with hemoglobins of less than 12 g/dL, he added.

"It is likely that the incidence of the problem of anemia in cancer will increase," Dr. Tchekmedyian predicted, as the overall population and particularly the number of people over age 55, increase. An estimated 2.5 million people over 55 years of age will develop cancer every year by the year 2020.