Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

Abstract

PURPOSE:

To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma.

PATIENTS AND METHODS:

Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status.

RESULTS:

The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively).

CONCLUSION:

In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

• Authors: Wendy R Cornett, Linda M McCall, Rebecca P Petersen, Merrick I Ross, Henry A Briele, R Dirk Noyes, Jeffrey J Sussman, William G Kraybill, John M Kane 3rd, H Richard Alexander, Jeffrey E Lee, Paul F Mansfield, James F Pingpank, David J Winchester, Richard L White Jr, Vijaya Chadaram, James E Herndon 2nd, Douglas L Fraker, Douglas S Tyler, American College of Surgeons Oncology Group Trial Z0020
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 25 Pg. 4196-201 (Sep 01 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16943537 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Alkylating
• Tumor Necrosis Factor-alpha
• Melphalan

Topics

• Adult
• Aged
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects)
• Chemotherapy, Cancer, Regional Perfusion (adverse effects, methods)
• Extremities
• Female
• Humans
• Hyperthermia, Induced
• Male
• Melanoma (drug therapy)
• Melphalan (administration & dosage, adverse effects)
• Middle Aged
• Patient Selection
• Skin Neoplasms (drug therapy)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (administration & dosage, adverse effects)
• United States