Growth Factors ReduceToxicity, Allow Greater DoseIntensity in Elderly PatientsWith Cancer

BETHESDA, MD-Older cancerpatients should receive adequateprophylaxis with growth factors toensure that they can receive full-dosechemotherapy without dose reductions,according to Ralph V. Boccia,MD.If doses are reduced or delayed becauseof cytopenia, the treatmentmight be less successful; in fact, thereare very few cases in which doses forthe fit elderly should be reduced: "Youwon't end up with the outcome, andyou will still end up with the toxicity,"said Dr. Boccia, director of research atthe Center for Cancer and Blood Disorders,Bethesda, Maryland.There is ample evidence, he said, toshow that age is not a contraindicationto standard-dose chemotherapy forlung, breast, colorectal, and prostatecancer, along with non-Hodgkin'slymphoma.Cancer patients more than 65 yearsof age are less tolerant of chemotherapy,and they have a higher risk ofadverse effects such as neutropeniaand anemia. However, fit older patientswho receive adequate prophylaxisnow appear to be able to toleratethe bone marrow suppression causedby their treatment.Benefits of Growth Factors"There are effective ways to copewith treatment-related toxic effects,"said Dr. Boccia. For example, multipletrials have shown that hematopoieticgrowth factors reduce the incidence ofneutropenia, and more importantlyneutropenic infections, vs no administrationof growth factors.In proposed guidelines, expertsrecommended that patients aged 70years or older receive hematopoieticgrowth factors such as filgrastim inany combination chemotherapy regimenthat has dose intensity equivalentto CHOP (cyclophosphamide[Cytoxan, Neosar]/doxorubicin HCl/vincristine [Oncovin]/prednisone) orAC (doxorubicin/cyclophosphamide).In addition, the experts sayhemoglobin (Hb) should be maintainedat 12 g/dL or above with erythropoieticagents (Oncology 14:221-227, 2000).For elderly patients, erythropoieticagents can help ameliorate fatigue,complications of anemia and chemotherapytoxicity. Studies (J Clin Oncol19:2865-2874, 2001) have shown thatcorrecting anemia this way may improvesurvival in cancer patients.Erythropoietic agents also havebeen shown to improve quality of lifein multiple studies, including a studyby Glaspy et al (The Oncologist 7:126-135, 2002), in which investigatorslooked at Functional Assessment ofCancer Therapy-Anemia (FACT-An)scores relative to Hb improvement inmore than 4,000 community-treatedcancer patients receiving epoetin alfa(Procrit). Glaspy et al found that evensmall increases in Hb yielded improvementsin quality of life. "This can evenoccur in patients with progressive dis-ease, if you correct anemia, which ispretty striking," Dr. Boccia said.CHOP-14 Plus G-CSF Superiorto CHOP-21Elderly patients may also benefitfrom dose intensification enabled byuse of growth factors. This was shownin a trial by the German High-GradeNon-Hodgkin's Lymphoma StudyGroup (DSHNHL) that suggested thatthe 14-day CHOP regimen could becomethe new standard regimen forNHL patients more than 60 years ofage.In the DSHNHL trial, presented atthe 2001 meeting of the American Societyof Hematology (abstract 3027),investigators randomized more than807 elderly patients (age range, 61 to75 years) with aggressive NHL to 6cycles of the typical CHOP-every-21-days schedule (CHOP-21), or one ofthree comparator arms: CHOP every21 days plus etoposide (CHOEP-21);dose-intensive CHOP every 14 days(CHOP-14) plus granulocyte colonystimulatingfactor (G-CSF [Neupogen])support; or dose-intensiveCHOP plus etoposide every 14 days(CHOEP-14) plus G-CSF support.Relative dose intensities were 95%for CHOEP-21 and 93% for CHOP-14 plus. "Clearly, they were able tomaintain dose intensity [by] givingcytokine therapy [with] these two regimens,"Dr. Boccia said.For standard CHOP-21, the completeresponse rate was 63.2%, comparedwith 77% for dose-intenseCHOP-14 with G-CSF support (P =.009). At a median of 40 months' observationtime, overall survival was49% for CHOP-21 and 64.3% forCHOP-14 (P = .04)."What was impressive was that theresponse rate looked quite good," saidDr. Boccia. "If you intensify using cytokinesupport, the response rate ishigher and overall survival appears tobe up."