Isolated limb perfusion with melphalan and tumor necrosis factor alpha for advanced melanoma and soft-tissue sarcoma.
BACKGROUND
Isolated limb perfusion (ILP) with melphalan is used in the treatment of advanced in-transit melanoma but has no real efficacy for irresectable soft tissue sarcomas arising in the extremities. The addition of tumor necrosis factor (TNF)-alpha may increase response rates for bulky melanoma and for sarcoma, but the potential for major systemic toxicity has limited its use.


METHODS
Between October 2000 and April 2004, 49 ILPs were performed with melphalan and TNF-alpha. All procedures were performed with continuous leakage monitoring and regional hyperthermia.


RESULTS
Forty-nine ILPs were performed for melanoma (n = 30), sarcoma (n = 16), or other tumors (n = 3). The most common indications were widespread in-transit disease for melanoma (n = 29) and irresectable primary disease for sarcoma (n = 9). Complete and partial responses for melanoma were 40% and 37%, and for sarcoma they were 20% and 33%. At a median follow-up of 14 months, 66% of melanoma patients who responded had not experienced local progression, compared with only 37% of sarcoma patients. Progression-free survival was significantly less for patients with sarcoma than melanoma (P = .0476). Four of 16 patients with sarcoma subsequently required amputation for progressive disease.


CONCLUSIONS
ILP with melphalan and TNF-alpha is a valuable treatment for advanced in-transit melanoma. Significant response rates were also seen in irresectable sarcoma, although the duration of response was limited.
Hayes
Andrew J
AJ
Department of Surgery, Sarcoma and Melanoma Unit, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom. andrew.hayes@rmh.nhs.uk
Neuhaus
Susan J
SJ
Clark
Matthew A
MA
Thomas
J Meirion
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan