Phase Ib study of NGR-hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours

British Journal of Cancer

Volumn 101, Issue 2, 2009, Pages 219-224

  Gregorc, V ^a   Santoro, A ^b   Bennicelli, E ^c   Punt, C J A ^d   Citterio, G ^a   Timmer Bonte, J N H ^d   Caligaris Cappio, F ^a   Lambiase, A ^e   Bordignon, C ^e   Van Herpen, C M L ^d  

^a SAN RAFFAELE HOSPITAL   (Italy)

^b HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^c UNIVERSITY OF GENOA   (Italy)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e MOLMED S P A   (Italy)

Author keywords

Doxorubicin; NGR hTNF; Vascular targeting agent

Indexed keywords

ASPARAGINYLGLYCINYLARGININE HUMAN TUMOR NECROSIS FACTOR; DOXORUBICIN; MICROSOMAL AMINOPEPTIDASE; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG; VASCULAR TARGETING AGENT; ANTINEOPLASTIC AGENT; HYBRID PROTEIN; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA, CNGRC FUSION PROTEIN, HUMAN; TUMOR NECROSIS FACTOR-ALPHA, CNGRC FUSION PROTEIN, HUMAN;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANEMIA; ANOREXIA; ARTICLE; ASTHENIA; BLOOD TOXICITY; CHILL; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; COUGHING; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; FEBRILE NEUTROPENIA; FEMALE; FEVER; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTRITIS; GENE OVEREXPRESSION; HEART EJECTION FRACTION; HUMAN; INSOMNIA; LEUKOPENIA; LOW DRUG DOSE; LUNG EMBOLISM; LYMPHOCYTOPENIA; MALE; MUCOSA INFLAMMATION; MULTICENTER STUDY; NAUSEA; NEUTROPENIA; PAIN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; SOLID TUMOR; THROMBOCYTOPENIA; VOMITING; METABOLISM; MIDDLE AGED; NEOPLASM;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOXORUBICIN; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; RECOMBINANT FUSION PROTEINS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 67650638995     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6605162     Document Type: Article

References (15)

1. Aderka D, Sorkine P, Abu-Abid S, Lev D, Setton A, Cope AP, Wallach D, Klausner J (1998) Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion. J Clin Invest 101: 650-659
2. Brett J, Gerlach H, Nawroth P, Steinberg S, Godman G, Stern D (1989) Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins. J Exp Med 169: 1977-1991
3. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72: 3666-3670
4. Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, Hagerty KL, Somerfield MR, Vaughn DJ, for the ASCO Cancer Survivorship Expert Panel (2007) American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol 25: 3991-4008
5. Corti A, Ponzoni M (2004) Tumor vascular targeting with tumor necrosis factor alpha and chemotherapeutic drugs. Ann N Y Acad Sci 1028: 104-112
6. Creaven PJ, Brenner DE, Cowens JW, Huben RP, Wolf RM, Takita H, Arbuck SG, Razack MS, Proefrock AD (1989) A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days. Cancer Chemother Pharmacol 23: 186-191
7. Curnis F, Sacchi A, Borgna L, Magni F, Gasparri A, Corti A (2000) Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol 18: 1185-1190
8. Curnis F, Sacchi A, Corti A (2002) Improving chemotherapeutic drug penetration in tumors by vascular targeting and barrier alteration. J Clin Invest 110: 475-482
9. Gallo-Stampino C, Rizzardi P, Toma S, Corti A, Scifo P, Citterio G, Gregorc V, Del Maschio A, Caligaris Cappio F, Bordignon C (2007) Safety and anticancer activity of low dose regimen of NGR-hTNF, a new vascular targeting agent, in solid advanced malignancies (NGR002 phase I trial). J Clin Oncol 25: 18s, (suppl; abstr 3540)
10. Gamm H, Lindemann A, Mertelsmann R, Herrmann F (1991) Phase I trial of recombinant human tumour necrosis factor alpha in patients with advanced malignancy. Eur J Cancer 27: 856-863
11. Horsman MR, Siemann DW (2006) Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 66: 11520-11539
12. Kwak EL, Clark JW, Chabner B (2007) Targeted agents: the rules of combination. Clin Cancer Res 13: 5232-5237
13. Rangel R, Sun Y, Guzman-Rojas L, Ozawa MG, Sun J, Giordano RJ, Van Pelt CS, Tinkey PT, Behringer RB, Sidman RL, Arap W, Pasqualini R (2007) Impaired angiogenesis in aminopeptidase N-null mice. Proc Natl Acad Sci USA 104: 4588-4593
14. Sacchi A, Gasparri A, Gallo-Stampino C, Toma S, Curnis F, Corti A (2006) Synergistic antitumor activity of cisplatin, paclitaxel, and gemcitabine with tumor vasculature-targeted tumor necrosis factor-alpha. Clin Cancer Res 12: 175-182
15. van Laarhoven H, Fiedler W, Desar IM, van Asten S, Marreaud S, Belli R, Bordignon C, Heerschap A, Punt CJ, van Herpen CM (2008) Phase I and DCE-MRI evaluation of NGR-TNF, a novel vascular targeting agent, in patients with solid tumors (EORTC 16041). J Clin Oncol 26: 158s, (suppl; abstr 3521)