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

David L. Bartlett, Grace Ma, H. Richard Alexander, Steven K. Libutti, Douglas L. Fraker

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2084-2090
Number of pages7
JournalCancer
Volume80
Issue number11
DOIs
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Melphalan
Reperfusion
Melanoma
Extremities
Tumor Necrosis Factor-alpha
Perfusion
Thiotepa
Mechlorethamine
Dactinomycin
Platinum
Dacarbazine
Skin
National Cancer Institute (U.S.)
Amputation

Keywords

  • Hyperthermia
  • In transit
  • Limb perfusion
  • Medical oncology
  • Melanoma
  • Melphalan
  • Metastases
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics. / Bartlett, David L.; Ma, Grace; Alexander, H. Richard; Libutti, Steven K.; Fraker, Douglas L.

In: Cancer, Vol. 80, No. 11, 01.12.1997, p. 2084-2090.

Research output: Contribution to journalArticle

Bartlett, David L. ; Ma, Grace ; Alexander, H. Richard ; Libutti, Steven K. ; Fraker, Douglas L. / Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics. In: Cancer. 1997 ; Vol. 80, No. 11. pp. 2084-2090.
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abstract = "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.",
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T1 - Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics

AU - Bartlett, David L.

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AU - Alexander, H. Richard

AU - Libutti, Steven K.

AU - Fraker, Douglas L.

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N2 - 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.

AB - 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.

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