title: Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma.
abstract: OBJECTIVE
  NGR-hTNF consists of human tumor necrosis factor alpha (hTNF-alpha) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting.
  
  
  METHODS
  Eligible patients had radiologically documented tumor progression and performance status < or = 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 microg/m(2) was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 microg/m(2) on a weekly basis.
  
  
  RESULTS
  In the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months.
  
  
  CONCLUSIONS
  The tolerability and disease control of NGR-hTNF 0.8 microg/m(2) weekly warrant additional evaluation in patients with advanced MPM.
authors.affiliation: Department of Oncology, Istituto Scientifico San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gregorc
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Zucali
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Citterio
authors.forename: Tommaso M
authors.initials: TM
authors.lastname: De Pas
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zilembo
authors.forename: Fabio
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: Matteo
authors.initials: M
authors.lastname: Simonelli
authors.forename: Gilda
authors.initials: G
authors.lastname: Rossoni
authors.forename: Anna
authors.initials: A
authors.lastname: Spreafico
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Viganò
authors.forename: Floriana
authors.initials: F
authors.lastname: Fontana
authors.forename: Filippo G
authors.initials: FG
authors.lastname: De Braud
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Lambiase
authors.forename: Claudio
authors.initials: C
authors.lastname: Bordignon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human