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
| Autor: | Papadia Francesco, Basso Valeria, Patuzzo Roberto, Maurichi Andrea, Di Florio Annabella, Zardi Luciano, Ventura Elisa, González-Iglesias Reinerio, Lovato Valeria, Giovannoni Leonardo, Tasciotti Annaelisa, Neri Dario, Santinami Mario, Menssen Hans D, De Cian Franco |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Aged 80 and over Male Leg Skin Neoplasms Dose-Response Relationship Drug Recombinant Fusion Proteins extremity melanoma targeted immunocytokine vascular targeting vasodisruptive therapy Hyperthermia Induced Middle Aged Drug Administration Schedule Treatment Outcome Chemotherapy Cancer Regional Perfusion Antineoplastic Combined Chemotherapy Protocols Humans Female Antineoplastic Agents Alkylating Melanoma Melphalan Aged |
| Zdroj: | Journal of surgical oncology |
| ISSN: | 1096-9098 |
| Popis: | 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. J. Surg. Oncol © 2012 Wiley Periodicals Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text