Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma.
BACKGROUND
L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients.


METHODS
Seven and 10 patients received 325 µg and 650 µg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure.


RESULTS
Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 µg that was durable at 12 months in four patients. No CR was seen at 325 µg of L19-TNF.


CONCLUSIONS
ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 µg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.
Department of Surgery (DI.C.M.I.), Genoa University, Genoa, Italy.
Francesco
F
Papadia
Valeria
V
Basso
Roberto
R
Patuzzo
Andrea
A
Maurichi
Annabella
A
Di Florio
Luciano
L
Zardi
Elisa
E
Ventura
Reinerio
R
González-Iglesias
Valeria
V
Lovato
Leonardo
L
Giovannoni
Annaelisa
A
Tasciotti
Dario
D
Neri
Mario
M
Santinami
Hans D
HD
Menssen
Franco
F
De Cian
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; C558733:L19mTNFalpha protein; D011993:Recombinant Fusion Proteins; D008558:Melphalan