The Emerging Role of Cytokines in the Treatment of Advanced Melanoma

Cytokine-based treatment regimens have been evaluated for advanced melanoma in a number of phase I and phase II trials within the last decade. Treatment with interleukin-2 (IL-2) as a single agent has resulted in response rates of approximately 15%, if a high dose of IL-2 is administered. Combination of interferon-α (IFNα) and high dose IL-2 yields response rates ranging from 10 to 41%. Response rates exceeding 50% have been reported with chemoimmunotherapy, if the treatment regimens included at least the three agents IL-2, IFNα and cisplatin. Recent randomized trials have evaluated the impact of these drugs on the survival of patients with advanced melanoma. The current ‘state of the art’ is discussed in this review.

[1]  R. Dummer,et al.  Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  C. Chastang,et al.  Randomised trial of interferon α-2a as adjuvant therapy in resected primary melanoma thicker than 1·5 mm without clinically detectable node metastases , 1998, The Lancet.

[3]  M. Binder,et al.  Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M. Gore,et al.  Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. , 1998, British Journal of Cancer.

[5]  C. Chastang,et al.  Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. , 1998, Lancet.

[6]  J. Kirkwood,et al.  Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D. Schadendorf,et al.  A randomized trial of IFNα/IL-2 with or without CDDP in advanced melanoma: An EORTC melanoma cooperative group trial , 1996 .

[8]  A. Buzaid,et al.  Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha. , 1996, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  A. Eggermont,et al.  Dose efficacy study of two schedules of high-dose bolus administration of interleukin 2 and interferon alpha in metastatic melanoma. , 1996, British Journal of Cancer.

[10]  C. Scheibenbogen,et al.  A phase II study of dacarbazine, cisplatin, interferon-alpha and high-dose interleukin-2 in 'poor-risk' metastatic melanoma. , 1996, European journal of cancer.

[11]  B. Zee,et al.  Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  C. Scheibenbogen,et al.  Prognostic factors for response and survival in patients with metastatic melanoma receiving immunotherapy , 1996, Melanoma research.

[13]  S. Legha,et al.  Evaluation of interleukin‐2 administered by continuous infusion in patients with metastatic melanoma , 1996, Cancer.

[14]  S. Rosenberg,et al.  Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  J. Becker,et al.  A multicenter phase II clinical trial using dacarbazine and continuous infusion lnterleukin‐2 for metastatic melanoma. Clinical data and immunomonitoring , 1995, Cancer.

[16]  Legha Ss,et al.  Combination of chemotherapy with interleukin-2 and interferon-alfa for the treatment of advanced melanoma. , 1994 .

[17]  R. Fisher,et al.  Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  N. Cascinelli,et al.  Results of adjuvant interferon study In WHO melanoma programme , 1994, The Lancet.

[19]  P. Queirolo,et al.  Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  R. Fisher,et al.  Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  S. Martino,et al.  A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin‐2 in metastatic malignant melanoma , 1993, Cancer.

[22]  R. Dillman,et al.  Inpatient continuous‐infusion interleukin‐2 in 788 patients with cancer the national biotherapy study group experience , 1993, Cancer.

[23]  P. Hersey,et al.  Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. , 1993, Melanoma research.

[24]  C. Balch,et al.  Cutaneous melanoma: prognosis and treatment results worldwide. , 1992, Seminars in surgical oncology.

[25]  C. Boni,et al.  Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. , 1992, The New England journal of medicine.

[26]  J. Richards,et al.  Sequential chemoimmunotherapy in the treatment of metastatic melanoma. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  W. Fridman,et al.  Lack of effect of tumour infiltrating lymphocytes in patients with metastatic melanoma who failed to respond to interleukin 2. , 1992, European journal of cancer.

[28]  M. Atkins,et al.  Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  J. Kirkwood.  Studies of interferons in the therapy of melanoma. , 1991, Seminars in oncology.

[30]  J. Monson,et al.  Clinical experience with the combined use of recombinant interleukin‐2 (IL2) and interferon alfa‐2a (IFNα) in metastatic melanoma , 1991, British journal of haematology.

[31]  E. Hersh,et al.  Phase II study of intravenous bolus recombinant interleukin-2 in advanced malignant melanoma: Southwest Oncology Group study. , 1991, Journal of the National Cancer Institute.

[32]  C. Falkson,et al.  Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  B. Redman,et al.  Sequential dacarbazine/cisplatin and interleukin-2 in metastatic melanoma: immunological effects of therapy. , 1991, Journal of immunotherapy.

[34]  J. Doroshow,et al.  Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  N. Barth,et al.  Recombinant interleukin-2 and adoptive immunotherapy alternated with dacarbazine therapy in melanoma: a National Biotherapy Study Group trial. , 1990, Journal of the National Cancer Institute.

[36]  S. Martino,et al.  A phase I‐II study of dacarbazine in combination with outpatient interleukin‐2 in metastatic malignant melanoma , 1990, Cancer.

[37]  S. Lakhani,et al.  Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit. , 1990, British Journal of Cancer.

[38]  S. Steinberg,et al.  Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  W. Linehan,et al.  Experience with the Use of High‐Dose Interleukin‐2 in the Treatment of 652 Cancer Patients , 1989, Annals of surgery.

[40]  N. Thatcher,et al.  Recombinant IL-2 given intra-splenically and intravenously in advanced malignant melanoma: a phase I/II study. , 1989, Cancer treatment reviews.

[41]  Legha Ss.  Current therapy for malignant melanoma. , 1989 .

[42]  S. Rodenhuis,et al.  Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study. , 1989, European Journal of Cancer and Clinical Oncology.

[43]  G. Marshall,et al.  Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. , 1987, The New England journal of medicine.

[44]  A. Chang,et al.  Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. , 1985, The New England journal of medicine.

[45]  S. Pestka,et al.  Modulation by recombinant DNA leukocyte (alpha) and fibroblast (beta) interferons of the expression and shedding of HLA- and tumor-associated antigens by human melanoma cells. , 1984, Journal of immunology.

[46]  A. Huang,et al.  DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma , 1980, Cancer.