title: Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies.
abstract: BACKGROUND
  asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 μg/m(2) as optimal biological and maximum-tolerated dose, respectively.
  
  
  METHODS
  Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 μg/m(2) in combination with capecitabine-oxaliplatin (XELOX).
  
  
  RESULTS
  Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy.
  
  
  CONCLUSIONS
  Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: S
authors.initials: S
authors.lastname: Mammoliti
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: V
authors.initials: V
authors.lastname: Andretta
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: E
authors.initials: E
authors.lastname: Bennicelli
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: F
authors.initials: F
authors.lastname: Caprioni
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: D
authors.initials: D
authors.lastname: Comandini
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: G
authors.initials: G
authors.lastname: Fornarini
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: A
authors.initials: A
authors.lastname: Guglielmi
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: A
authors.initials: A
authors.lastname: Pessino
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: S
authors.initials: S
authors.lastname: Sciallero
authors.affiliation: Medical Oncology Unit, Ospedale San Martino, Genoa.
authors.forename: A F
authors.initials: AF
authors.lastname: Sobrero
authors.affiliation: Clinical Development, MolMed, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Mazzola
authors.affiliation: Clinical Development, MolMed, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Lambiase
authors.affiliation: Clinical Development, MolMed, Milan; Hematology, Università Vita-Salute San Raffaele, Milan, Italy. Electronic address: claudio.bordignon@hsr.it.
authors.forename: C
authors.initials: C
authors.lastname: Bordignon
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil