Benefits of Erythropoietic Agents May Extend Beyond Improving Fatigue and Quality of Life

July 1, 2003

DENVER, Colorado-Treatingcancer-related anemia improves qualityof life and may have other potential therapeuticbenefits for cancer patients, accordingto speakers at a cancer-relatedanemia symposium presented in conjunctionwith the 28th Annual Congress of theOncology Nursing Society. The expertpanel also discussed the need for earlierintervention with flexible dosing regimensand outlined potential future applicationsof erythropoietic agents.

DENVER, Colorado-Treatingcancer-related anemia improves qualityof life and may have other potential therapeuticbenefits for cancer patients, accordingto speakers at a cancer-relatedanemia symposium presented in conjunctionwith the 28th Annual Congress of theOncology Nursing Society. The expertpanel also discussed the need for earlierintervention with flexible dosing regimensand outlined potential future applicationsof erythropoietic agents.Changing Transfusion Guidelines
"Before 1980, red blood cell transfusionswere given frequently because therewasn't much worry about transfusions.We would give people transfusions at ahemoglobin level under 10 g/dL," saidDavid H. Henry, MD, clinical associateprofessor of medicine at the University ofPennsylvania School of Medicine in Philadelphia.In the 1980s, concerns abouttransfusion-related diseases and the scarceblood supply were responsible for changingtransfusion guidelines to 8 g/dL."Now we're starting to think aboutearly intervention, perhaps under 12g/dL, and treating up to and including 12g/dL, as well as the potential therapeuticefficacy in cognitive functioning and possiblelinks to survival," Dr. Henry added.The impact of fatigue on quality of lifehas been documented. Based on data citedby Dr. Henry, 30% of patients experiencedaily fatigue, 57% have difficulty in socializingwith family and friends becauseof fatigue, and 75% have to alter theirwork status because of their fatigue.

In 2002, Crawford and colleaguesshowed that quality of life improves withincreasing hemoglobin levels (Figure 1)."When you take hemoglobins from 6 g/dLall the way up to 12 g/dL, quality of lifesteadily improves," Dr. Henry suggested.The greatest functional improvement occurredamong patients at 10 g/dL or higher,and most of the improvement was at11, 12, and up to 13 g/dL. "Females aresupposed to be at 12 g/dL and above, andmales are supposed to be at 13.5 g/dL andabove, so there must be a reason thatnature wants us at that set point," Dr.Henry stated.Erythropoietic Agents
Today, agents such as epoetin alfa(Procrit) and darbepoetin alfa (Aranesp)can reduce the need for transfusions andsignificantly improve fatigue and qualityof life among cancer patients. Approvedin 1993, epoetin alfa significantly reducesthe need for transfusions, causes a rapidrise in hemoglobin level by about 1 g ormore by week 4 (Figure 2), can be titratedfor early dose escalation after 4 weeks, andimproves quality of life independent oftumor response.Approved in 2002, darbepoetin alfaalso reduces the need for transfusions,causes a rise in hemoglobin levels (Figure3), and improves quality of life in responders.It has a longer half-life thanepoetin alfa but less epoetin alfa-receptorbinding. Titration can be undertaken after6 weeks. In addition, therapy may improvetumor response rate, patient survival,and cognitive function.However, Dr. Henry noted that aboutone-third of patients do not respond toerythropoietic agents, and the reason forthis lack of response is unknown.Dosing Issues, Prognostic Significance
Lillian M. Nail, PhD, RN, professorand senior scientist at the Oregon Healthand Science University School of Nursingin Portland, explored dosing issues andreviewed research on the effects of epoetinalfa on quality of life, patient response,and treatment outcome. The approvedof patients with head and neck cancer(91% of whom were men) who were treatedwith neoadjuvant chemoradiation followedby surgery.In their secondary analysis, researchersdivided the population into threegroups. Group 1 consisted of patients withpretreatment hemoglobin levels of at least14.5 g/dL. These patients did not receiveepoetin alfa because it had not been approved.Group 2 included patients with apretreatment hemoglobin level of less than14.5 g/dL. These patients received epoetinalfa during all or part of their therapy,whenever their hemoglobin levels droppedbelow 12.5 g/dL. Group 3 had a pretreatmenthemoglobin level of less than 14.5g/dL but did not receive epoetin alfa becauseit had not been approved.The 2-year survival for the group withthe high pretreatment hemoglobin levelswas 81%, compared with 60% for thegroup with the lower pretreatment hemoglobinlevels who did not receive epoetinalfa. Group 2 also had a significantly longermedian survival than did group 3, andthe 2-year survival for group 2 was 88%.These results suggest that low pretreatmenthemoglobin levels are a negativeprognostic factor for survival, although alarger prospective trial is needed for firmconclusions about the data, Dr. Barsevickadded.Cognitive Benefits
There is also evidence to suggest thatepoetin alfa can attenuate or prevent cognitivedysfunction in cancer patients undergoingchemotherapy. "Even at standarddoses, adjuvant chemotherapyappears to have distressing effects on someaspects of cognitive functioning, includingconcentration and memory, as well asattention, speed of information processing,and motor speed," Dr. Barsevick explained.These effects are independent ofmood changes or self-reported problems.O'Shaughnessy and colleagues examinedthe effects of epoetin alfa in breastcancer patients undergoing anthracyclinetreatment. They found that 18% of patientsreceiving epoetin alfa experiencedimprovement in cognitive function beforethe fourth cycle of chemotherapy,compared with only 2% of the placebogroup. Moreover, only 4.5% of the epoetinalfa group experienced deteriorationin cognitive function, compared with almost14.0% of the placebo group. Theseresults demonstrate that for breast cancerpatients receiving chemotherapy, treatmentwith weekly epoetin alfa improvedor prevented decline in cognitive functionin comparison to a placebo control.Furthermore, epoetin alfa may have aneuroprotective effect, shielding the brainfrom the negative effects of chemotherapy.Animal studies of induced brainischemia and preliminary studies ofpatients suffering acute ischemic strokealso support a direct neuroprotective effectof epoetin alfa, concluded Dr.Barsevick.