TNFa-based isolated hyperthermic limb perfusion (HILP) in the treatment of limb recurrent melanoma: update 16 years after its first clinical application.
Hyperthermic Limb Perfusion (HILP) with Tumor Necrosis Factor alpha (TNFalpha) and interferon gamma (IFNgamma) was pioneered by Liénard and Lejeune in 1988. TNFalpha was empirically employed at a dosage of 3-4 mg that is ten times the systemic maximum tolerated dose (MTD). Sixteen years after its first clinical application more than 300 patients have been treated and some clarifications can be made regarding three major questions: the real role of IFNgamma, the TNFalpha dose and eligibility criteria for patient selection. A randomized phase II study has demonstrated that IFNgamma does not increase significantly the efficacy but does increase side-effects. Experimental and clinical results seem to indicate that patients with bulky melanoma disease can really benefit from TNFalpha HILP carried out with only 1 mg.
Di Filippo
F
F
Regina Elena National Cancer Institute, Rome, Italy. difilippo@ifo.it
Cavaliere
F
F
Garinei
R
R
Anzà
M
M
Di Angelo
P
P
Psaila
A
A
Piarulli
L
L
Callopoli
A
A
Bruno
P
P
Di Filippo
S
S
Priore
F
F
D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D005121:Extremities; D006801:Humans; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000494:pharmacology; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy*; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma