This Article 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 Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garrido-Laguna, I. Articles by Espinós, J. Search for Related Content PubMed PubMed Citation Articles by Garrido-Laguna, I. Articles by Espinós, J. Related Articles Related Reply Related Article Social Bookmarking                            What's this?

Is There Any Reason to Delay Introduction of Tumor Necrosis Factor in the Management of In-Transit Metastasis of Unresectable Melanoma?

Clinica Universitaria, Universidad de Navarra, Pamplona, Spain

To the Editor:

The recent publication by Cornett et al¹ tries to shed some light on the role that the addition of tumor necrosis factor (TNF) to melfalan hyperthermic isolated limb perfusion may have in the management of unresectable in-transit disease in melanoma patients.

We are concerned about the statistical design of this trial because is not based on an intention-to-treat analysis. As the authors refer, 133 patients were enrolled in this trial, 17 patients (12%) were excluded from the analysis for several reasons, and interestingly up to 14 of these patients had already begun the study treatment. In this article the authors do not mention if patients were evenly excluded from both arms, and even if that is the case, an intention-to-treat analysis should have been done (this analysis is generally favored because it avoids bias associated with nonrandom loss of participants).²

Furthermore, based on the expected time to peak response, the primary objective of this study was tumor response at 3 months. As the authors concluded, this study did not show a difference between melfalan versus melfalan plus TNF at 3 months, but looking closer at the data presented, we may come to the conclusion that there is a clear trend to increased response rate at 6 months in the melfalan plus TNF arm, with complete response rates nearly doubling that obtained in the melfalan alone arm (42% v 20%). Although this data do not reach statistical significance (P < .1), we do not know the confidence intervals and we consider that results should not be reported solely as P values.

We do not know to what extent the inclusion of patients with greater tumor burden in the melfalan plus TNF arm may have played a role in eluting a benefit from addition of TNF.

As opposed to the conclusion of the authors that addition of TNF-alpha should be considered in patients who respond poorly to initial perfusion of melfalan alone, we consider that a benefit from the addition of TNF to melfalan may have been undetected by this study. Since we have the suspicion that addition of TNF may increase response rate at 6 months and no single category of adverse events was statistically more frequent in the TNF arm, we consider that introduction of TNF from the beginning is still an option.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Cornett WR, McCall LM, Petersen RP, et al: 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. J Clin Oncol 24:4196-4201, 2006[Abstract/Free Full Text]

2. Lachin JL: Statistical considerations in the intent-to-treat principle. Control Clin Trials 21:526, 2000[CrossRef][Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Reply

• In Reply
  Wendy R. Cornett, Linda M. McCall, Rebecca P. Petersen, James E. Herndon, II, and Douglas S. Tyler
  JCO 2007 25: 1149-1151 [Full Text]

Related Article

• 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, and Douglas S. Tyler
  JCO 2006 24: 4196-4201 [Abstract] [Full Text]

This Article 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 Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garrido-Laguna, I. Articles by Espinós, J. Search for Related Content PubMed PubMed Citation Articles by Garrido-Laguna, I. Articles by Espinós, J. Related Articles Related Reply Related Article Social Bookmarking                            What's this?