title: Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy.
abstract: BACKGROUND
  NGR-hTNF consists of human tumour necrosis factor (hTNF) fused with the tumour-homing peptide Asp-Gly-Arg (NGR), which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. Preclinical antitumour activity was observed even at low doses. We evaluated the activity and safety of low-dose NGR-hTNF in colorectal cancer (CRC) patients failing standard therapies.
  
  
  METHODS
  Thirty-three patients with progressive disease at study entry received NGR-hTNF 0.8 μg/m(2) given intravenously every 3 weeks. The median number of prior treatment regimens was three (range, 2-5). One-quarter of patients had previously received four or more regimens and two-thirds targeted agents. Progression-free survival (PFS) was the primary study objective.
  
  
  RESULTS
  NGR-hTNF was well tolerated. No treatment-related grade 3 to 4 toxicities were detected, most common grade 1 to 2 adverse events being short-lived, infusion-time related chills (50.0%). One partial response and 12 stable diseases were observed, yielding a disease control rate of 39.4% (95% CI, 22.9-57.8%). Median PFS and overall survival were 2.5 months (95% CI, 2.1-2.8) and 13.1 months (95% CI, 8.9-17.3), respectively; whereas in patients who achieved disease control the median PFS and overall survival were 3.8 and 15.4 months, respectively. In an additional cohort of 13 patients treated at same dose with a weekly schedule, there was no increased toxicity and 2 patients experienced PFS longer than 10 months.
  
  
  CONCLUSIONS
  Based on tolerability and preliminary evidence of disease control in heavily pretreated CRC patients, NGR-hTNF deserves further evaluation in combination with standard chemotherapy.
authors: Department of Oncology, Istituto Clinico Humanitas, Rozzano, Italy.
authors: Armando
authors: A
authors: Santoro
authors: Lorenza
authors: L
authors: Rimassa
authors: Alberto F
authors: AF
authors: Sobrero
authors: Giovanni
authors: G
authors: Citterio
authors: Francesco
authors: F
authors: Sclafani
authors: Carlo
authors: C
authors: Carnaghi
authors: Anna
authors: A
authors: Pessino
authors: Francesco
authors: F
authors: Caprioni
authors: Valeria
authors: V
authors: Andretta
authors: Maria Chiara
authors: MC
authors: Tronconi
authors: Giovanna
authors: G
authors: Finocchiaro
authors: Gloria
authors: G
authors: Rossoni
authors: Angela
authors: A
authors: Zanoni
authors: Chiara
authors: C
authors: Miggiano
authors: Gian-Paolo
authors: GP
authors: Rizzardi
authors: Catia
authors: C
authors: Traversari
authors: Federico
authors: F
authors: Caligaris-Cappio
authors: Antonio
authors: A
authors: Lambiase
authors: Claudio
authors: C
authors: Bordignon
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human