LITTLE ROCK—For patients with cancer-related fatigue, "the first line of treatment, in my opinion, is to increase their hemoglobin levels so that they can begin an exercise program," noted William Evans, PhD. "Cancer patients suffering from primary fatigue should not be advised to increase the amount of daily rest. Rather, they should be counseled to carry out aerobic exercise," he explained. Dr. Evans serves as director, nutrition, metabolism, and exercise, and professor of geriatrics, physiology, and nutrition at the University of Arkansas for Medical Sciences in Little Rock.

An exercise physiologist by training, Dr. Evans noted that fatigue is related to reduced aerobic capacity, which can be measured by VO₂max (cardiac output times the arterial/venous oxygen difference). VO₂max varies enormously, with values ranging from 60 mL/kg/min. and up for professional athletes, to 50 and below for sedentary individuals. In cancer patients, VO₂max levels have been measured below 20 mL/kg/min.

Benefits of rHuEPO

Dr. Evans reviewed one randomized prospective study examining the protective effects of recombinant erythropoietin(Drug information on erythropoietin) (rHuEPO) on metabolic and exercise capacity in cancer patients losing weight. The study involved 108 cancer patients, most with gastrointestinal cancers, randomized to oral indomethacin alone or with rHuEPO.

Despite being "somewhat complicated by a huge drop-out rate," the results clearly showed that hemoglobin levels and exercise capacity continued to drop in patients who did not receive rHuEPO, while patients who received it maintained relatively high hemoglobin levels of about 13 g/dL and increased their exercise capacity (see Figure 1). "The conclusion was that anemia is effectively overcome by rHuEPO in unselected cancer patients. Treatment of anemia preserved physical function, defined as exercise power and whole body metabolic efficiency," Dr. Evans said. "There is a remarkably strong relationship between change in VO₂max and change in hemoglobin," he continued, "and at submaximal exercise capacities, restoring hemoglobin levels results in increased cardiac output and a change in heart rate and lactate."

Cancer fatigue is probably due not only to anemia, but also to loss of muscle mass resulting from cachexia, and severe deconditioning, Dr. Evans said. "Many cancer patients who become anemic and lose muscle mass are likely to be very inactive. Increasing their hematocrit may allow cancer patients to participate in a regular conditioning program to resolve this issue of severe deconditioning."

Reviewing the somewhat sparse literature on the subject, Dr. Evans found that cancer patients losing weight or suffering from severe fatigue had greatly reduced VO₂max, equivalent only to the oxygen cost of simply walking at a normal pace of about 2½ miles per hour. "Most of the activities of daily living are well above the so-called anaerobic threshold of most cancer patients," Dr. Evans said. "That tells us two things: that their fatigue is related to their anemia and low VO₂max, but also their severe deconditioning." The anaerobic threshold is the point when muscles begin producing more lactic acid(Drug information on lactic acid) than they consume and spill lactic acid into the blood, increasing respiration rate. Above the threshold it is extremely difficult to work without becoming fatigued.