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Letter to the Editor

In Reply

Department of Psychiatry and Behavioral Sciences and Department of Medicine, Memorial Sloan-Kettering Cancer Center, NewYork, NewYork, USA

Correspondence: Paul B. Chapman, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. Telephone: 212–639–5015; Fax: 212–794–4352; e-mail: chapmanp{at}mskcc.org

Received March 2, 2006; accepted for publication March 29, 2006.

Physicians and patients who are not in the melanoma field will find Tarhini and colleagues’ thorough review of the adjuvant high-dose interferon results indicative of how complex this issue has become [1]. The purpose of our article was to help patients make sense of the published data. For patients faced with the decision of whether to undergo high-dose interferon treatment or to opt only for observation, only the first two randomized trials—E1684 and E1690—provide directly relevant information. Although E1684 initially showed a small overall survival advantage for the interferon group that barely reached statistical significance, as Tarhini and colleagues acknowledge, this small survival advantage lost statistical significance with slightly longer follow-up. They speculate that this could be a result of patients having died of other causes, but there have been no data presented to support this. The general consensus of the melanoma field [2–6] is that these trials demonstrated a small improvement in time to relapse but that individually, in a pooled analysis by Kirkwood and colleagues [7], in an independent review [4], and in a meta-analysis [3], these trials have not provided evidence for an improvement in overall survival.

Tarhini and colleagues discuss a third randomized trial—E1694—but that trial does not address the underlying question facing a patient trying to decide what to do. In that trial, patients in the experimental group received an experimental vaccine while the control group received high-dose interferon. The trial was designed to see if the vaccine improved median survival or the cure rate over interferon. Although the prior two trials had demonstrated no overall long-term survival advantage associated with high-dose interferon compared with observation, in E1694 at 16 months follow-up the vaccine group was inferior to the interferon group for both progression-free survival and overall survival. It was clear that the vaccine was not an improvement over high-dose interferon, and the trial was stopped. Because the median follow-up was relatively short, it will be interesting to see whether the difference in overall survival between the two groups continues to be significant with longer follow-up. In any event, these results do not directly inform a patient’s decision of whether to take high-dose interferon or opt for observation.

We therefore must disagree with Dr. Tarhini’s assertion that treatment with high-dose interferon leads to an improvement in overall survival. We believe the data do not support this conclusion. Although there may be other reasons for patients to elect to undergo adjuvant high-dose interferon treatment, as we discussed in our article, patients should understand that there is no established improvement in overall survival compared with observation.

	DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

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Dr. Chapman has acted as a consultant for Schering-Plough.

	REFERENCES

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1. Tarhini A, Shipe-Spotle J, DeMark M et al. Response to "Helping Melauoma patients decide whether to choose adjuvant high-dose interferon- 2b." The Oncologist 2006;11:538–539.[Free Full Text]
2. Eggermont AM, Suciu S, MacKie R et al. Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial. Lancet 2005;366:1189–1196.[Medline]
3. Wheatley K, Ives N, Hancock B et al. Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev 2003;29:241–252.[CrossRef][Medline]
4. Lens MB, Dawes M. Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 2002;20:1818–1825.[Abstract/Free Full Text]
5. Schuchter LM. Adjuvant interferon therapy for melanoma: high-dose, low-dose, no dose, which dose? J Clin Oncol 2004;22:7–10.[Free Full Text]
6. Hancock BW, Wheatley K, Harris S et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol 2004;22:53–61.[Abstract/Free Full Text]
7. Kirkwood JM, Manola J, Ibrahim J et al. A pooled analysis of Eastern Cooperative Oncology Group and Intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res 2004;10:1670–1677.[Abstract/Free Full Text]

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