title: Comparing the efficacy and safety of fixed versus weight-based dosing of epoetin alpha in anemic cancer patients receiving platinum-based chemotherapy.
abstract: Fixed dosing is potentially more convenient than weight-based dosing for both patients and physicians. Therefore, this open-label, randomized (1:1), multicenter study was conducted to compare the effectiveness, safety, and quality-of-life benefits of fixed vs. weight-based dosing of epoetin alpha in anemic cancer patients undergoing chemotherapy. Five hundred forty-six anemic patients undergoing platinum-based chemotherapy for solid malignancies were enrolled. Patients received epoetin alpha, either a fixed dose of 10,000 IU or a weight-based dose of 150 IU/kg, administered subcutaneously 3 times weekly for up to 12 weeks. Endpoints were transfusion requirements over days 29-84, change in hemoglobin (Hb) level from baseline, and change in quality-of-life (QOL) scores from baseline as measured using the Cancer Linear Analog Scale (CLAS). Five hundred and thirty-two patients received at least 1 dose of epoetin alpha, and 510 of these (255 in each treatment group) were considered evaluable for efficacy. At day 84, rates for freedom from transfusion were similar between the fixed-dose and the weight-based dose group (84% vs. 87%, respectively, p=0.32), as calculated by the lifetable method. These rates were also similar between patients in the 45-63 kg weight group receiving the fixed 10,000 IU dose or 7,000-9,000 IU on a per-weight basis (83% vs. 87%, respectively), and those in the 70-100 kg weight group receiving the fixed 10,000 IU dose or 11,000-15,000 IU on a per-weight basis (85% vs. 83%, respectively). Mean Hb increases from baseline to last observation were 2.10 g/dl [95% confidence intervals (CI95) 1.85-2.35] in the 10,000 IU group (from 9.64-11.74 g/dl) and 2.06 g/dl (CI95 1.82-2.30) in the 150 IU/kg group (from 9.70-11.76 g/dl). QOL results were similar for both groups and cumulative data have been reported. For 275 patients (in both groups combined) with CLAS QOL scores both at baseline and 29-98 days thereafter, the QOL index (average of scores for the 3 QOL parameters: energy level, ability to do daily activities and overall QOL) increased by 10.4 mm (CI95 7.5-13.2), from 46.2 mm at baseline to 56.6 mm at the final observation. QOL improvements were directly associated with Hb increases (p<0.001, multiple linear regression analysis) within all chemotherapy response classes. Epoetin alpha was well tolerated in both groups. Fixed (10,000 IU) and weight-based (150 IU/kg) dosing regimens of epoetin alpha demonstrated similar efficacy in maintaining freedom from transfusion, increasing Hb levels, and improving QOL in anemic cancer patients undergoing platinum-based chemotherapy. QOL improvements were directly associated with Hb increases. These findings support the use of a fixed-dose regimen of epoetin alpha, which may offer greater convenience for physicians and patients than weight-based dosing with this agent.
authors.affiliation: Oncology Department, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Granetto
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Andrea
authors.initials: A
authors.lastname: Martoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pezzella
authors.forename: Franco
authors.initials: F
authors.lastname: Testore
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Mattioli
authors.forename: Maria
authors.initials: M
authors.lastname: Lampignano
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Tacconi
authors.forename: Stella
authors.initials: S
authors.lastname: Porrozzi
authors.forename: Giampietro
authors.initials: G
authors.lastname: Gasparini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mantovani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001803:Blood Transfusion; D001835:Body Weight; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006454:Hemoglobins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000627:therapeutic use*; D011788:Quality of Life; D011897:Random Allocation; D011994:Recombinant Proteins; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D010984:Platinum; D000068817:Epoetin Alfa