title: Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy.
abstract: BACKGROUND
  Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy.
  
  
  METHODS
  Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study.
  
  
  RESULTS
  Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups.
  
  
  CONCLUSIONS
  Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.
authors.affiliation: Medical Oncology, "La Sapienza" University, viale del Policlinico, 00161 Rome, Italy. enrico.cortesi@uniroma1.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Mancuso
authors.forename: Adolfo
authors.initials: A
authors.lastname: De Pasquale Ceratti
authors.forename: Nicolina
authors.initials: N
authors.lastname: Pizzardi
authors.forename: Giuliana
authors.initials: G
authors.lastname: D'Auria
authors.forename: Caterina
authors.initials: C
authors.lastname: Accettura
authors.forename: Patrizia
authors.initials: P
authors.lastname: Beccaglia
authors.forename: Daniela
authors.initials: D
authors.lastname: Bertelletti
authors.forename: Filippo
authors.initials: F
authors.lastname: De Marinis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa