title: Survival, response and immune effects in a prospectively randomized study of dose strategy for alpha-N1 interferon.
abstract: Several tumour sites have now demonstrated objective responses to alpha interferons in a diversity of doses and schedules. Since effectiveness should be enhanced with the identification of an optimal dose strategy, we undertook a prospectively randomized study to compare an intermittent high dose escalating strategy (HDS) vs. a fixed low dose treatment in relation to clinical outcome and laboratory correlates of immune function. HDS patients received interferon alpha-N1 (lymphoblastoid interferon) 5M units m-2 by continuous i.v. infusion over 24 h, escalating by 5 M units m-2 day-1 as tolerated over 10 days, and repeated every 28 days. The low dose strategy (LDS) consisted of a fixed dose of 2 M units m-2 by intramuscular injection daily for 28 days, then daily for 7 days every other week. There were 53 evaluable patients. In keeping with earlier preliminary results there was evidence of improved immune function for HDS patients. They demonstrated a significant increase in the number of CD2+ (sheep red blood cell binding) cells and CD4+ (helper-inducer/suppressor-inducer) cells along with enhanced activity of natural killer cell, and mixed leukocyte culture activity. In addition to improved immune function, HDS patients survived longer than LDS (P = 0.04). Analysis of survival in relation to response suggested that monitoring of minor responses may be of interest for biological agents such as interferon.
authors.affiliation: Department of Advanced Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: H K
authors.initials: HK
authors.lastname: Silver
authors.forename: J M
authors.initials: JM
authors.lastname: Connors
authors.forename: S
authors.initials: S
authors.lastname: Kong
authors.forename: K A
authors.initials: KA
authors.lastname: Karim
authors.forename: J J
authors.initials: JJ
authors.lastname: Spinelli
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000401:mortality; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage* / Q000633:toxicity; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000401:mortality; D011446:Prospective Studies; D011897:Random Allocation
chemical_list: D007370:Interferon Type I