Early Intervention With Epoetin Prevents Anemia in NSCLC Patients

VANCOUVER, Canada-Recombinant human erythropoietin(epoetin alfa, Epogen, Procrit) administeredto patients with non-small-celllung cancer (NSCLC) who are undergoingchemotherapy has been foundto significantly reduce the incidence ofanemia, compared with best supportivecare, and to improve quality of life.Robert Milroy, MD, of Stobhill GeneralHospital, Glasgow, United Kingdom,presented the study findings atthe 10th World Conference on LungCancer (abstract O-253)."The biggest reduction in quality oflife occurs when Hb drops from 12 to11 g/dL," Dr. Milroy said. "We wantedto see if it is possible to prevent anemiain patients by early intervention withepoetin alfa [to possibly] improve qualityof life and even survival."The international, phase III studyrandomized 380 patients with stageIIIb (48%) or stage IV (51%) (1%unspecified) NSCLC who were receivingcisplatin (Platinol)-based or carboplatin(Paraplatin)-based chemotherapy.Eligibility criteria includedhemoglobin of 15 g/dL or less for menand 14 g/dL or less for women.Patients were randomized on a 1:1basis to receive 10,000 IU epoetin alfasubcutaneously three times weekly orbest supportive care, which includedchemotherapy. Treatment with epoetinalfa was initiated when hemoglobindropped below 13 g/dL in men andbelow 12 g/dL in women.Patients whose hemoglobin levelswere at 13 g/dL (men) and 12 g/dL(women) at study entry (the immediatetreatment group) received epoetinalfa immediately. Other patients startedchemotherapy and began epoetinalfa when their hemoglobin droppedbelow the trigger points (the delayedtreatment group).Epoetin alfa was administered forup to 4 weeks following the last cycle ofchemotherapy. The study duration was28 weeks. The mean hemoglobin levelat study baseline was 12.7 g/dL (range7.7 to 15.3 g/dL). Quality of life wasassessed with the FACT-An (FunctionalAssessment of Cancer Therapy-Anemia) subscale.Study ResultsResults show that overall, 8.9% ofpatients treated with epoetin alfa requiredblood transfusions, comparedwith 24.3% of those receiving best supportivecare (P < .0001). This representsa transfusion reduction of morethan 50%.There was also a significant differencebetween the active treatment andbest-supportive-care groups with respectto stabilized hemoglobin. In theentire study population, patients treatedwith epoetin alfa had stabilized hemoglobinat greater than 12.5 g/dLthroughout the study period, whereaspatients in the best-supportive-caregroup experienced a steady decline(P < .001).A subgroup analysis of the immediateand delayed epoetin alfa treatmentgroups showed that the strategy of earlyuse did work, "particularly the earlytreatment in patients with low hemoglobinat the outset," Dr. Milroy said.Immediate epoetin alfa treatmentmaintained hemoglobin levels duringchemotherapy, despite significantlyfewer blood transfusions (P < .001),he said.Data on the delayed-treatmentgroup showed a fall in hemoglobininitially, followed by stabilization. "Thepoint is that in the treated patients,epoetin alfa was able to maintain hemoglobinof between 12.5 and 12.7g/dL. In the best-supportive-care controlarm, the patients became significantlyanemic," Dr. Milroy said. "Thestrategy to prevent anemia worked."Quality of LifeImmediate epoetin alfa intervention,but not delayed treatment, reducedthe decline in quality of life."This may be because the delayedgroup had started with normal hemoglobinand then drifted down by overa gram before they could start epoetinalfa," Dr. Milroy said.The most striking survival finding,he said, was that the patients in theimmediate- treatment group, who wereanemic at the study outset, had muchworse survival regardless of epoetinalfa treatment, compared with patientsin the delayed treatment group. Theresults show a highly statistically significantdifference between the immediateand delayed treatment groups'survival of 24.8% and 48.1%, respectively(P < .0001)."We all know hemoglobin is an individualprognostic factor, but this is astriking change," Dr. Milroy said. "Wedidn't see any benefits from epoetinalfa either in the immediate or thedelayed arms in terms of survival benefits.We were disappointed by that."However, the data showed a 20% improvementin overall survival amongpatients with baseline hemoglobin of13 g/dL or more (male) and 12 g/dL ormore (female), compared with patientswho had lower baseline hemoglobin."The strategy works; epoetin alfawas able to keep patients' hemoglobinlevels up and prevent anemia, and thatwas consistent for both the immediateand delayed treatment groups," Dr.Milroy said.