title: Response to thalidomide in multiple myeloma: impact of angiogenic factors.
abstract: Thalidomide has antiangiogenic and immunomodulatory effects, mediated by several cytokines such as vascular endothelial growth factor (VEGF), fibroblastic growth factor (FGF-2), hepatocyte growth factor (HGF), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Although extramedullary plasmacytomas (EMP) have a high vascularization, the response of these patients to thalidomide is controversial. Thirty-eight patients with refractory/relapsed MM were treated with thalidomide. Eleven patients had EMP when therapy was initiated. Serum specimens were obtained in patients before treatment was started and at the time of maximum response in responding patients or at thalidomide discontinuation in non-responders. Serum levels of VEGF, HGF and FGF-2 were determined in 18 patients whereas IL-6 and TNF-alpha were measured in 19 patients. Sixteen of the 38 patients (42%) responded to thalidomide. The response rate was significantly higher in patients without EMP (59% vs 0%, p = 0.0006 ). VEGF serum levels were significantly higher in responding patients. In contrast, baseline serum levels of HGF were significantly lower in responders. Neither VEGF nor HGF serum levels showed correlation with the presence of EMP. Baseline TNF-alpha serum levels were significantly lower in responding patients and in those without EMP. The serum levels of FGF-2 and IL-6 did not correlate with response to treatment or presence of EMP.
authors.affiliation: Institut Clínic de Malaties Hemato-Oncològiques, Hematology Department, Institut d' Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Cibeira
authors.forename: Marta
authors.initials: M
authors.lastname: Segarra
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
authors.forename: Xavier
authors.initials: X
authors.lastname: Filella
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: María
authors.initials: M
authors.lastname: Rozman
authors.forename: Leonor
authors.initials: L
authors.lastname: Arenillas
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010954:Plasmacytoma / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D013792:Thalidomide / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D016207:Cytokines; D013792:Thalidomide