Point: Interferon-α for Adjuvant Therapy for Melanoma Patients

Authors:
Michael S. Sabel Department of Surgery, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan

Search for other papers by Michael S. Sabel in
Current site
Google Scholar
PubMed Close
 MD
and
Vernon K. Sondak Department of Surgery, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan

Search for other papers by Vernon K. Sondak in
Current site
Google Scholar
PubMed Close
 MD
Volume/Issue:
Volume 2: Issue 1
Online Publication Date:
Jan 2004
DOI:
https://doi.org/10.6004/jnccn.2004.0004
Full access

Interferon-α is possibly the most controversial adjuvant therapy for any solid tumor, and multiple trials involving varying doses, routes, schedules, and formulations of interferon-α have increased the confusion. Clinicians are left in a quandary, because high-dose interferon-α-2b (HDI) remains the only FDA-approved adjuvant therapy for high-risk melanoma. Of the three prospective randomized trials involving high-dose interferon-α-2b, all show a significant improvement in disease-free survival and two show a significant improvement in overall survival. Despite this strong evidence, data from studies involving alternate doses, concerns regarding cost and toxicity, and the promise of future therapies have led opponents of interferon to overlook these results. Based on the available clinical evidence, however, high-dose interferon should be offered as standard care for patients with high-risk, resected melanoma. Informed patients who have elected to forego interferon and patients with lower risk lesions can be offered participation in clinical trials with a no-treatment control arm.

Correspondence: Michael S. Sabel, MD, University of Michigan Comprehensive Cancer Center, 3304 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109. E-mail: msabel@umich.edu
  • Collapse
  • Expand
Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
  • 1

    Balch CM, Buzaid AC, Soong S-J et al.. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635–3648.

  • 2

    Dickler MN, Coit DG, Myers ML. Adjuvant therapy of malignant melanoma. Surg Oncol Clin N Am 1997; 6:793–812.

  • 3

    Pfeffer LM, Dinarello CA, Herberman RB et al.. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons. Cancer Res 1998;58:2489–2499.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Frank SJ, Meyers M. Interferon as adjuvant therapy for high risk melanoma. Melanoma Lett 1995; 13:1–4.

  • 5

    Legha SS. Current therapy for malignant melanoma. Semin Oncol 1989;16:34–44.

  • 6

    Steiner A, Wolf CH, Pehamberger H. Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma and r-IFN alpha + cimetidine) in disseminated malignant melanoma. J Cancer Res Clin Oncol 1987;113:459–465.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Eggermont AM. The role interferon-alpha in malignant melanoma remains to be defined. Eur J Cancer 2001;37:2147–2153.

  • 8

    Punt CJA, Eggermont AM. Adjuvant interferon-alpha for melanoma revisited: news from old and new studies. Ann Oncol 2001;12:1633–1666.

  • 9

    Lens MB, Dawes M. Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 2002;20:1818–1825.

  • 10

    Wheatley K, Hancock B, Gore M. Interferon-alpha as adjuvant therapy for melanoma: a meta-analysis of the randomized trials (Abstract). Proc Am Soc Clin Oncol 2001;20:349a.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Kirkwood JM, Manola J, Ibrahim J et al.. Pooled analysis of four ECOG/Intergroup trials of high-dose interferon alpha-2b (HDI) in 1916 patients with high-risk resected cutaneous melanoma (Abstract). Proc Am Soc Clin Oncol 2001; 20:350a.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Thome' SD, Loprinzi CL, Heldebrandt MP. Determination of potential adjuvant systemic therapy benefits for patients with resected cutaneous melanoma. Mayo Clin Proc 2002;77:913–917.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Cascinelli N, Bufalino R, Morabito A, Mackie R. Results of adjuvant interferon study in WHO melanoma programme (letter). Lancet 1994;343:913–914.

  • 14

    Creagan ET, Dalton RJ, Ahmann DL et al.. Randomized, surgical adjuvant clinical trial of recombinant interferon alpha-2a in selected patients with malignant melanoma.J Clin Oncol 1995;13:2776–2783.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Pehamberger H, Soyer HP, Steiner A et al.. Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol 1998;16(4):1425–1429.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Grob JJ, Dreno B, de la Salmoniere P et al.. Randomised trial of interferon alfa-2a as adjuvant therapy in resected primary melanoma thicker than 1.5mm without clinically detectable node metastases. Lancet 1998;351:1905–1910.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Hancock BW, Wheatley K, Harrison G et al.. Aim high: Adjuvant interferon in melanoma (high risk), a United Kingdom Cooordinating Committee on Cancer Research (UKCCCR) randomized study of observation versus adjuvant low-dose extended duration intereron alpha-2a in high risk resected malignant melanoma (Abstract). Proc Am Soc Clin Oncol 2001;20:349a.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Kleeberg UR, Brocker EB, Lejeune FJ et al.. Adjuvant trial in melanoma patients comparing rIFN-α to rIFN-γ to Iscador to a control group after curative resection of high risk primary (>3mm or regional lymph node metastasis (EORTC 18871). Eur J Cancer 1999; 35 (Suppl 4):S82.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Cameron DA, Cornbleet MC, Mackie RM et al.. Adjuvant interferon alpha 2b in high risk melanoma—the Scottish study. Br J Cancer 2001;84:1146–1149.

  • 20

    Kirkwood JM, Ibrahim JG, Sondak VK et al.. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 2000;18:2444–2458.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Eggermont AMM, Gore M. A critical appraisal of the role of interferon-α in the treatment of malignant melanoma. Principles and Practice of Biologic Therapy of Cancer Updates. Philadelphia: Lippincott Williams and Wilkins, 2002: p 3.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Itri LM, Sherman MI, Palleroni AV et al.. Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon-alpha 2a. J Interferon Res 1989;9(suppl 1):S9–S15.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Speigel RJ, Jacobs SL, Treuhaft MS. Anti-interferon antibodies to interferon-alpha 2b: Results of comparative assays and clinical perspective. J Interferon Res 1989;9(suppl 1):S17–S24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Wussow PV, Jakschies D, Freund M et al.. Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha. Br J Haematol 1991;78:210–216.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Kokoschka EM, Trautinger F, Knobler RM et al.. Long-term adjuvant therapy of high risk malignant melanoma with interferon a2b. J Invest Dermatol 1990;95:S193–197.

  • 26

    Cascinelli N. Evaluation of efficacy of adjuvant rIFN-α 2a in melanoma patients with regional node metastases (Abstract). Proc Am Soc Clin Oncol 1994;14:410.

  • 27

    Rusciani L, Petraglia S, Alotto M et al.. Postsurgical adjuvant therapy for melanoma. Evaluation of a 3-year randomized trial with recombinant interferon-alpha after 3 and 5 years of follow-up. Cancer 1997;79:2354–2360.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Kirkwood JM, Strawderman MH, Ernstoff MS et al.. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996;14:7–17.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Kirkwood JM, Ibrahim JG, Sosman JA et al.. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol 2001;19:2370–2380.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Livingston PO, Wong GY, Adluri S et al.. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 1994;12:1036–1044.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Rodenhuis S, Bontenbal M, Beex LVAM et al.. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med 2003;349:7–16.

  • 32

    Tallman MS, Gray R, Robert NJ et al.. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med 2003;349:17–26.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Elfenbein GJ. Stem-cell transplantation for high-risk breast cancer. N Engl J Med 2003;349:80–82.

  • 34

    Kilbridge KL, Weeks JC, Sober AJ et al.. Patient preferences for adjuvant interferon alfa-2b treatment. J Clin Oncol 2001;19:812–823.

  • 35

    Spira AI, Ettinger DS. The use of chemotherapy in soft-tissue sarcomas. Oncologist 2002;7:348–359.

  • 36

    Davidson NE. Ongoing US cooperative groups trials using taxanes in the adjuvant setting. Clin Breast Cancer 2002;3(Suppl 2):S53–S58.

  • 37

    Saltz LB, Minsky B. Adjuvant therapy of cancers of the colon and rectum. Surg Clin North Am 2002;82:1035–1058.

  • 38

    Cole BF, Gelber RD, Kirkwood JM et al.. Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 1996;14:2666–2673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Hillner BE. Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma. Eur J Cancer 1998;34(suppl 3):S18–S21.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Hillner BE, Kirkwood JM, Atkins MB et al.. Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on projections from Eastern Cooperative Oncology Group 1684. J Clin Oncol 1997;15:2351–2358.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Gonzalez-Larriba JL, Serrano S, Alvarez-Mon M et al.. Cost-effectiveness analysis of interferon as adjuvant therapy in high-risk melanoma patients in Spain. Eur J Cancer 2000;36:2344–2352.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Cook J, Zitelli JA. Treating patients with melanoma with interferon (letter). Arch Dermatol 1997;133:387.

  • 43

    Russell-Jones R. Interferon-α therapy for melanoma. Clin Exp Dermatol 2000;25:1–6.

  • 44

    Morton DL, Hsueh EC, Essner R et al.. Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann Surg 2002;236:438–449.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Morton DL, Barth A. Vaccine therapy for malignant melanoma. CA Cancer J Clin 1996;46:225–244.

  • 46

    Hsueh EC, Essner R, Foshag LJ et al.. Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma. Ann Surg Oncol 2002;9:486–492.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Sondak VK, Liu PY, Tuthill RJ et al.. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. J Clin Oncol 2002;20:2058–2066.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Sosman JA, Unger JM, Liu PY et al.. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. J Clin Oncol 2002;20:2067–2075.

    • PubMed
    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2004 by the National Comprehensive Cancer Network 2004
Page Numbers:
8
Article Category:
Research Article
Received:
12 Aug 2003
Accepted:
31 Oct 2003
Print Publication Date:
01 Jan 2004
Online Publication Date:
Jan 2004
Keywords:
Interferon-α; carcinoma; adjuvant therapy; melanoma; immunotherapy

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 597 446 4
PDF Downloads 101 32 3
EPUB Downloads 0 0 0