title: A phase II trial of pegylated interferon alpha-2b therapy for polycythemia vera and essential thrombocythemia: feasibility, clinical and biologic effects, and impact on quality of life.
abstract: BACKGROUND
  Conventional interferon-alpha (IFN) is an effective treatment for patients with myeloproliferative disorders. However, many patients discontinue therapy because of side effects.
  
  
  METHODS
  In this 24-month, Phase II feasibility study of pegylated interferon alpha-2b (PEG-IFN) treatment, a starting dose of 0.5 microg/kg per week was received by 21 patients with polycythemia vera (PV) and 21 patients with essential thrombocythemia (ET). The treatment objective, a complete platelet response (CR), was a platelet count<400x10(9)/L in symptomatic patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera-1 (PRV-1) messenger RNA expression was analyzed prior to and during therapy. Quality of life (QoL) was investigated by using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire.
  
  
  RESULTS
  At 6 months, 29 of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was not related to diagnosis, gender, or previous therapy. Nineteen patients completed the planned 2-year treatment in CR. No thromboembolic or bleeding complications were observed. Phlebotomy requirements were reduced in the majority of patients with PV. Five of 14 patients (36%) who initially were positive for PRV-1 achieved normalized PRV-1 expression under PEG-IFN treatment. Side effects were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19 patients reported any side effects at 2 years. The QLQ-C30 revealed clinically significant impairments in several aspects of QoL at 6 months; however, at 2 years, QoL measurements were not different from baseline.
  
  
  CONCLUSIONS
  PEG-IFN effectively reduced platelet counts in 29 of 42 patients, but only 19 patients maintained a CR at 2 years. The reversal of PRV-1 positivity noted in a subset of patients suggested that PEG-IFN may have an effect on the malignant clone. PEG-IFN is a valuable therapeutic alternative for patients who tolerate its initial side effects.
authors.affiliation: Department of Medicine, Stockholm South Hospital, Stockholm, Sweden, and Department of Medicine, Roskilde University Hospital, Denmark. jan.samuelsson@sodersjukhuset.se
authors.forename: Jan
authors.initials: J
authors.lastname: Samuelsson
authors.forename: Hans
authors.initials: H
authors.lastname: Hasselbalch
authors.forename: Oystein
authors.initials: O
authors.lastname: Bruserud
authors.forename: Snezana
authors.initials: S
authors.lastname: Temerinac
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Brandberg
authors.forename: Mats
authors.initials: M
authors.lastname: Merup
authors.forename: Olle
authors.initials: O
authors.lastname: Linder
authors.forename: Magnus
authors.initials: M
authors.lastname: Bjorkholm
authors.forename: Heike L
authors.initials: HL
authors.lastname: Pahl
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegard
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004337:Drug Carriers; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007519:Isoantigens / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010976:Platelet Count; D011087:Polycythemia Vera / Q000188:drug therapy*; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011788:Quality of Life; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013922:Thrombocytosis / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; C407242:CD177 protein, human; D004337:Drug Carriers; D058851:GPI-Linked Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007519:Isoantigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b