This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cornett, W. R. Articles by Tyler, D. S. Search for Related Content PubMed Articles by Cornett, W. R. Articles by Tyler, D. 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

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

From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Pennsylvania, Philadelphia, PA; Duke University Medical Center, Durham; Carolinas Medical Center, Charlotte, NC; University of Illinois at Chicago, Chicago; Evanston Northwestern Healthcare, Evanston, IL; Latter Day Saints Hospital, Salt Lake City, UT; University of Cincinnati Medical Center, Cincinnati, OH; Roswell Park Cancer Institute, Buffalo, NY; Warren Grant Magnuson Clinical Center, and National Institutes of Health, Bethesda, MD

Address reprint requests to Douglas S. Tyler, MD, Duke University Medical Center, Box 3118, Durham, NC 27710; e-mail: tyler002{at}acpub.duke.edu

Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-) 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- 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- arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF- 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- 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- arm (P = .435 and P = .890, respectively).

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

Supported by Grant No. U10 CA076001 from the National Cancer Institute.

Presented at the 2005 Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, GA, March 4, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				G. M. Beasley, R. P. Petersen, J. Yoo, N. McMahon, T. Aloia, W. Petros, G. Sanders, T.-Y. Cheng, S. K. Pruitt, H. Seigler, et al. Isolated Limb Infusion for In-Transit Malignant Melanoma of the Extremity: A Well-Tolerated but Less Effective Alternative to Hyperthermic Isolated Limb Perfusion Ann. Surg. Oncol., August 1, 2008; 15(8): 2195 - 2205. [Abstract] [Full Text] [PDF]

				C. R. Rossi, F. Russano, S. Mocellin, V. Chiarion-Sileni, M. Foletto, P. Pilati, L. G. Campana, A. Zanon, G. F. Picchi, M. Lise, et al. TNF-Based Isolated Limb Perfusion Followed by Consolidation Biotherapy with Systemic Low-dose Interferon Alpha 2b in Patients with In-transit Melanoma Metastases: A Pilot Trial Ann. Surg. Oncol., April 1, 2008; 15(4): 1218 - 1223. [Abstract] [Full Text] [PDF]

				F. J. Lejeune and A. M.M. Eggermont Hyperthermic Isolated Limb Perfusion With Tumor Necrosis Factor Is a Useful Therapy for Advanced Melanoma of the Limbs J. Clin. Oncol., April 10, 2007; 25(11): 1449 - 1450. [Full Text] [PDF]

				W. R. Cornett, L. M. McCall, R. P. Petersen, J. E. Herndon II, and D. S. Tyler In Reply J. Clin. Oncol., April 10, 2007; 25(11): 1450 - 1451. [Full Text] [PDF]

				I. Garrido-Laguna, M. Ponz, and J. Espinos Is There Any Reason to Delay Introduction of Tumor Necrosis Factor in the Management of In-Transit Metastasis of Unresectable Melanoma? J. Clin. Oncol., March 20, 2007; 25(9): 1149 - 1149. [Full Text] [PDF]

				W. R. Cornett, L. M. McCall, R. P. Petersen, J. E. Herndon II, and D. S. Tyler In Reply J. Clin. Oncol., March 20, 2007; 25(9): 1149 - 1151. [Full Text] [PDF]