title: The first clinical pilot study of roquinimex (Linomide) in cancer patients with special focus on immunological effects.
abstract: Roquinimex (Linomide) has been demonstrated to suppress tumor growth in animal models. The effect is at least in part related to enhanced numbers and activity of natural killer (NK) cells. In this clinical pilot study, roquinimex was given at increasing doses (0.05 mg/kg to 0.6 mg/kg) to 13 patients (performance status 0-3) with various malignant disorders. Immunology parameters were followed and side effects were observed during the study. The plasma pharmacokinetics of roquinimex was studied at the 0.2 mg/kg dose level. The clinical side effects were dominated by musculoskeletal discomfort, nausea, and pain. No significant hematological or biochemical toxicity was observed. Pharmacokinetic analysis at the 0.2 mg/kg dose level revealed a Cmax of 4.0 mumol/L at tmax of 1.2 hr and an elimination half-life of 42 hr. Increased numbers of phenotypic NK cells, activated T (DR+CD4+) cells, and monocytes were observed after administration of roquinimex compared with pretreatment values. Roquinimex seems to be an active immunomodulator with manageable toxicity. Further exploration of therapeutic efficacy is warranted.
authors.affiliation: Department of Oncology, University Hospital, Uppsala, Sweden.
authors.forename: J C
authors.initials: JC
authors.lastname: Bergh
authors.forename: T H
authors.initials: TH
authors.lastname: Tötterman
authors.forename: B C
authors.initials: BC
authors.lastname: Termander
authors.forename: K A
authors.initials: KA
authors.lastname: Strandgarden
authors.forename: P O
authors.initials: PO
authors.lastname: Gunnarsson
authors.forename: B I
authors.initials: BI
authors.lastname: Nilsson
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006912:Hydroxyquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D006912:Hydroxyquinolines; C045282:roquinimex