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

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, H. Richard Alexander, Jeffrey E. Lee, Paul F. Mansfield, James F. Pingpank, David J. Winchester, Richard L. White, Vijaya Chadaram, James E. Herndon, Douglas L. Fraker, Douglas S. Tyler

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-α) 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-α 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-α arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-α 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-α 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-α arm (P = .435 and P = .890, respectively). Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-α to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-α plus melphalan was associated with a higher complication rate.

Original languageEnglish
Pages (from-to)4196-4201
Number of pages6
JournalJournal of Clinical Oncology
Volume24
Issue number25
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Fingerprint

Melphalan
Multicenter Studies
Extremities
Tumor Necrosis Factor-alpha
Perfusion
Arm
Melanoma
Amputation
Therapeutics
Random Allocation
Upper Extremity
Disease Progression
Lower Extremity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Cornett, Wendy R.; McCall, Linda M.; Petersen, Rebecca P.; Ross, Merrick I.; Briele, Henry A.; Noyes, R. Dirk; Sussman, Jeffrey J.; Kraybill, William G.; Kane, John M.; Alexander, H. Richard; Lee, Jeffrey E.; Mansfield, Paul F.; Pingpank, James F.; Winchester, David J.; White, Richard L.; Chadaram, Vijaya; Herndon, James E.; Fraker, Douglas L.; Tyler, Douglas S.

In: Journal of Clinical Oncology, Vol. 24, No. 25, 01.09.2006, p. 4196-4201.

Research output: Contribution to journalArticle

Cornett, WR, McCall, LM, Petersen, RP, Ross, MI, Briele, HA, Noyes, RD, Sussman, JJ, Kraybill, WG, Kane, JM, Alexander, HR, Lee, JE, Mansfield, PF, Pingpank, JF, Winchester, DJ, White, RL, Chadaram, V, Herndon, JE, Fraker, DL & Tyler, DS 2006, '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', Journal of Clinical Oncology, vol. 24, no. 25, pp. 4196-4201. https://doi.org/10.1200/JCO.2005.05.5152
Cornett, Wendy R. ; McCall, Linda M. ; Petersen, Rebecca P. ; Ross, Merrick I. ; Briele, Henry A. ; Noyes, R. Dirk ; Sussman, Jeffrey J. ; Kraybill, William G. ; Kane, John M. ; Alexander, H. Richard ; Lee, Jeffrey E. ; Mansfield, Paul F. ; Pingpank, James F. ; Winchester, David J. ; White, Richard L. ; Chadaram, Vijaya ; Herndon, James E. ; Fraker, Douglas L. ; Tyler, Douglas S. / 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. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 25. pp. 4196-4201.
@article{d6e7db85515245b3822ca1a58e533c84,
title = "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-α) 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-α 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-α arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-α 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-α 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-α arm (P = .435 and P = .890, respectively). Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-α to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-α plus melphalan was associated with a higher complication rate.",
author = "Cornett, {Wendy R.} and McCall, {Linda M.} and Petersen, {Rebecca P.} and Ross, {Merrick I.} and Briele, {Henry A.} and Noyes, {R. Dirk} and Sussman, {Jeffrey J.} and Kraybill, {William G.} and Kane, {John M.} and Alexander, {H. Richard} and Lee, {Jeffrey E.} and Mansfield, {Paul F.} and Pingpank, {James F.} and Winchester, {David J.} and White, {Richard L.} and Vijaya Chadaram and Herndon, {James E.} and Fraker, {Douglas L.} and Tyler, {Douglas S.}",
year = "2006",
month = "9",
day = "1",
doi = "10.1200/JCO.2005.05.5152",
language = "English",
volume = "24",
pages = "4196--4201",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "25",

}

TY - JOUR

T1 - Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor

T2 - American College of Surgeons Oncology Group trial Z0020

AU - Cornett, Wendy R.

AU - McCall, Linda M.

AU - Petersen, Rebecca P.

AU - Ross, Merrick I.

AU - Briele, Henry A.

AU - Noyes, R. Dirk

AU - Sussman, Jeffrey J.

AU - Kraybill, William G.

AU - Kane, John M.

AU - Alexander, H. Richard

AU - Lee, Jeffrey E.

AU - Mansfield, Paul F.

AU - Pingpank, James F.

AU - Winchester, David J.

AU - White, Richard L.

AU - Chadaram, Vijaya

AU - Herndon, James E.

AU - Fraker, Douglas L.

AU - Tyler, Douglas S.

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-α) 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-α 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-α arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-α 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-α 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-α arm (P = .435 and P = .890, respectively). Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-α to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-α plus melphalan was associated with a higher complication rate.

AB - Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-α) 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-α 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-α arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-α 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-α 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-α arm (P = .435 and P = .890, respectively). Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-α to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-α plus melphalan was associated with a higher complication rate.

UR - http://www.scopus.com/inward/record.url?scp=33748662393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748662393&partnerID=8YFLogxK

U2 - 10.1200/JCO.2005.05.5152

DO - 10.1200/JCO.2005.05.5152

M3 - Article

C2 - 16943537

AN - SCOPUS:33748662393

VL - 24

SP - 4196

EP - 4201

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 25

ER -