Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics

• Published in: Cancer Vol. 80; no. 11; pp. 2084 - 2090
• Main Authors: Bartlett, David L., Ma, Grace, Alexander, H. Richard, Libutti, Steven K., Fraker, Douglas L.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01-12-1997; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Arm; Biological and medical sciences; Dermatology; Female; Humans; hyperthermia; Hyperthermia, Induced; in transit; Leg; limb perfusion; Male; medical oncology; Medical sciences; melanoma; Melanoma - drug therapy; melphalan; Melphalan - administration & dosage; metastases; Middle Aged; Perfusion - methods; Retrospective Studies; Skin; Skin Neoplasms - drug therapy; Treatment Outcome; tumor necrosis factor; Tumor Necrosis Factor-alpha - administration & dosage; Tumors of the skin and soft tissue. Premalignant lesions; Antineoplastic agent; Human; Relapse; Cytokine; Lower limb; Malignant tumor; Chemotherapy; Reperfusion; Tumor necrosis factor; Melphalan; Malignant melanoma; End; Negative therapeutic reaction
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19971201)80:11<2084::AID-CNCR7>3.0.CO;2-X

BACKGROUND
This retrospective study evaluated the benefit of using tumor necrosis factor (TNF) and melphalan administered via an isolated limb perfusion (ILP) in a series of patients with metastatic melanoma who failed initial ILP with chemotherapeutics.
METHODS
Seventeen patients with extremity melanoma who underwent prior ILP with conventional chemotherapeutics (10 with melphalan; 4 with platinum; 2 with platinum, dacarbazine, thiotepa, actinomycin D, and nitrogen mustard; and 1 with thiotepa, actinomycin D, and nitrogen mustard) and had local recurrences were treated with a 90‐minute isolated hyperthermic limb reperfusion with melphalan (10 mg/L limb volume) plus TNF (2‐6 mg). Five prior ILPs were adjuvant and 12 were therapeutic.
RESULTS
Reperfusion was associated with an overall 94% response rate and a 65% complete response (CR) rate. Of the patients who failed an initial ILP with melphalan alone the overall response rate was 90% after the reperfusion with TNF and melphalan. In patients who failed an initial ILP with agents other than melphalan the CR rate was 100% after ILP with TNF and melphalan. TNF/melphalan isolated limb reperfusion was found to be more effective in terms of CR after initial ILP regimens that did not utilize melphalan (100% CR after nonmelphalan ILP vs. 50% CR after melphalan ILP [P = 0.04]). Regional toxicity was comprised of mild skin blistering and peeling in 47% of patients. One patient developed Grade 3 (based on National Cancer Institute Common Toxicity Criteria) skin necrosis, and one developed Grade 5 muscle and nerve toxicity, requiring an amputation.
CONCLUSIONS
Isolated limb reperfusion with TNF and melphalan can be performed safely with response rates similar to those of other trials of single perfusions. Repeat ILP using TNF and melphalan in patients with melanoma who have failed prior ILP with chemotherapeutics is justified. The utility of TNF (vs. melphalan alone) will be defined in ongoing Phase III trials. Cancer 1997; 80:2084‐90. © 1997 American Cancer Society.
Repeat isolated limb perfusion with tumor necrosis factor and melphalan after failure of initial isolated limb perfusion using chemotherapeutics alone for patients with in‐transit melanoma is associated with a response rate similar to the best response rates achieved with initial isolated limb perfusion with any available regimens.