Isolated limb perfusion in locally advanced cutaneous melanoma.
Isolated limb perfusion (ILP) is a well-established locoregional procedure to deliver high doses of cytostatics to an extremity with multiple in-transit lesions from cutaneous melanoma, with minimal systemic and mild local toxicity. This approach is quite sophisticated and requires accurate monitoring of systemic leakage and of the temperature of the affected limb in order to avoid major systemic and local side effects. Mephalan (L-PAM) is considered the reference drug, although complete responses are reported in only about 50% of patients. Since the early 1990s, tumor necrosis factor-alpha (TNF-alpha) was administered with melphalan in ILP aiming to improve the therapeutic index of this procedure. However, despite the impressive results reported, its role still remains controversial, seemingly confined to large tumor bulk. Fotemustine ILP was proposed as a less toxic alternative to L-PAM, after the results of a pilot experience claiming similar response rates with less local toxicity. A formal phase 1-2 study is now underway to confirm these findings. More straightforward procedures, such as isolated limb infusion, are appealing, as they seem capable of achieving good response rates, are easily repeatable, and are less costly. Larger series are required to validate such results. As potential agents to be delivered through ILP, new vasoactive drugs and agents with new mechanisms of action that interplay with chemotherapy, as well as virus-mediated gene therapy, are being developed.
Rossi
Carlo Riccardo
CR
Department of Surgical and Oncological Sciences Clinica Chirurgica II, University of Padova, Padova, Italy.
Foletto
Mirto
M
Pilati
Pierluigi
P
Mocellin
Simone
S
Lise
Mario
M
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015316:Genetic Therapy; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D009367:Neoplasm Staging; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D010865:Pilot Projects; D012074:Remission Induction; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D014409:Tumor Necrosis Factor-alpha; C054368:fotemustine; D008558:Melphalan