Cancer Treatment Reviews
Volume 37, Issue 2 , Pages 133-142 , April 2011

Current and future adjuvant immunotherapies for melanoma: Blockade of cytotoxic T-lymphocyte antigen-4 as a novel approach

  • Sanjiv S. Agarwala

      Affiliations

    • Medical Oncology and Hematology, St. Luke’s Cancer Center, 801 Ostrum Street, Bethlehem, PA 18015, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 610 954 2145; fax: +1 610 954 2108.
    • ,
  • Steven J. O’Day

      Affiliations

    • The Angeles Clinical and Research Institute, 2001 Santa Monica Blvd, Suite 560W, Santa Monica, CA 90404, USA
    • Tel.: +1 310 582 7975; fax: +1 310 582 7979.

Received 31 March 2010 ,Accepted 14 June 2010.

References 

  1. American Cancer Society, Atlanta, GA. Cancer Facts & Figures 2009. <http://www.cancer.org/downloads/STT/500809web.pdf> [accessed 10.09.2009].
  2. Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature. 2007;445:851–857
  3. World Health Organization. <http://www.who.int/uv/faq/skincancer/en/index1.html> [accessed 29.01.2010].
  4. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol. 2004;150:179–185
  5. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–6206
  6. Francken AB, Accortt NA, Shaw HM, et al. Follow-up schedules after treatment for malignant melanoma. Br J Surg. 2008;95:1401–1407
  7. Lee CC, Faries MB, Wanek LA, Morton DL. Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol. 2008;26:535–541
  8. Morton DL, Thompson JF, Cochran AJ, et al. MSLT Group. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–1317
  9. Agrawal S, Kane JM, Guadagnolo BA, Kraybill WG, Ballo MT. The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma. Cancer. 2009;115:5836–5844
  10. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology-melanoma, V.1.2010. <www.nccn.org>.
  11. Korn EL, Liu PY, Lee SJ, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008;26:527–534
  12. Agarwala SS. Current systemic therapy for metastatic melanoma. Expert Rev Anticancer Ther. 2009;9:587–595
  13. Tarhini AA, Agarwala SS. Cutaneous melanoma: available therapy for metastatic disease. Dermatol Ther. 2006;19:19–25
  14. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010. [Epub ahead of print].
  15. Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351:998–1012
  16. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–399
  17. Rosenberg SA. Why perform sentinel-lymph-node biopsy in patients with melanoma?. Nat Clin Pract Oncol. 2008;5:1
  18. Phan GQ, Messina JL, Sondak VK, Zager JS. Sentinel lymph node biopsy for melanoma: indications and rationale. Cancer Control. 2009;16:234–239
  19. Wright BE, Scheri RP, Ye X, et al. Importance of sentinel lymph node biopsy in patients with thin melanoma. Arch Surg. 2008;143:892–900
  20. Eggermont AM, Gore M. Randomized adjuvant therapy trials in melanoma: surgical and systemic. Semin Oncol. 2007;34:509–515
  21. Lawson DH. Choices in adjuvant therapy of melanoma. Cancer Control. 2005;12:236–241
  22. Verma S, Quirt I, McCready D, et al. Systematic review of systemic adjuvant therapy for patients at high risk for recurrent melanoma. Cancer. 2006;106:1431–1442
  23. Bajetta E. Adjuvant use of interferon α2b is not justified in patients with stage IIb/III melanoma. Nat Clin Pract Oncol. 2008;5:4–5
  24. Hauschild A. Adjuvant interferon alfa for melanoma: new evidence-based treatment recommendations?. Curr Oncol. 2009;16:3–6
  25. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. 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
  26. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U. Eastern Cooperative Oncology Group. 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
  27. 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
  28. 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
  29. Eggermont AM, Suciu S, Ruka W, et al. EORTC 18961: post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results. J Clin Oncol. 2008;26(15s):[abstract 9004]
  30. Lens MB, Dawes M. Interferon alfa therapy for malignant melanoma: a systemic review of randomized controlled trials. J Clin Oncol. 2002;20:1818–1825
  31. Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-α for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev. 2003;29:241–252
  32. Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. J Clin Oncol. 2002;20:1311–1318
  33. Hauschild A, Gogas H, Tarhini A, et al. Practical guidelines for the management of interferon-α-2b side effects in patients receiving adjuvant treatment for melanoma: expert opinion. Cancer. 2008;112:982–994
  34. Schuchter LM. Adjuvant interferon therapy for melanoma: high-dose, low-dose, no dose, which dose?. J Clin Oncol. 2004;22:7–10
  35. Grob JJ, Dreno B, de la Salmonière P, et al. Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet. 1998;351:1905–1910
  36. 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;16:1425–1429
  37. Cascinelli N, Belli F, MacKie RM, Santinami M, Bufalino R, Morabito A. Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial. Lancet. 2001;358:866–869
  38. 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
  39. Kleeberg UR, Suciu S, Bröcker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha-2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3mm) or regional lymph node metastasis. Eur J Cancer. 2004;40:390–402
  40. 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
  41. Hauschild A, Weichenthal M, Rass K, et al. Prospective randomized multicenter adjuvant Dermatologic Cooperative Oncology Group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma. J Clin Oncol. 2009;27:3496–3502
  42. Agarwala SS, Gray RJ, Wong MKK. Duration of high-dose interferon alfa-2b regimen for resected high-risk melanoma. J Clin Oncol. 2009;27:e82–e83
  43. Kirkwood JM, Tarhini AA, Moschos SJ, Panelli MC. Adjuvant therapy with high-dose interferon alpha 2b in patients with high-risk stage IIB/III melanoma. Nat Clin Pract Oncol. 2008;5:2–3
  44. Critchley-Thorne RJ, Simons DL, Yan N, et al. Impaired interferon signaling is a common immune defect in human cancer. Proc Natl Acad Sci USA. 2009;106:9010–9015
  45. Pectasides D, Dafni U, Bafaloukos D, et al. Randomized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma. J Clin Oncol. 2009;27:939–944
  46. Mohr P, Hauschild A, Enk A, et al. Intermittent high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: an interim analysis of a randomized phase III study (NCT00226408). J Clin Oncol. 2008;26(15s):[abstract 9040]
  47. Chiarion-Sileni V, Del Bianco P, Romanini A, et al. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomised phase III Italian Melanoma Inter-group trial (IMI-Mel.A.) [ISRCTN75125874]. BMC Cancer. 2006;6:44
  48. ClinicalTrials.gov. High-dose interferon alfa in treating patients with stage II or stage III melanoma. <http://www.clinicaltrials.gov/show/NCT00003641> [accessed 09.02.2010].
  49. Hauschild A, Schadendorf D, Garbe C, Ugurel S, Kähler KC. New promises in the adjuvant, and palliative treatment of melanoma. Cancer Treat Res. 2007;135:277–292
  50. Dummer R, Mangana J. Long-term pegylated interferon-alpha and its potential in the treatment of melanoma. Biologics. 2009;3:169–182
  51. Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372:117–126
  52. Bottomley A, Coens C, Suciu S, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2009;27:2916–2923
  53. Janku F, Kurzrock R. Adjuvant interferon in high-risk melanoma: end of the era?. J Clin Oncol. 2010;28:e15–e16
  54. Hauschild A, Weichenthal M, Balda BR, et al. Prospective randomized trial of interferon alfa-2b and interleukin-2 as adjuvant treatment for resected intermediate- and high-risk primary melanoma without clinically detectable node metastasis. J Clin Oncol. 2003;21:2883–2888
  55. Garbe C, Radny P, Linse R, et al. Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis. Ann Oncol. 2008;19:1195–1201
  56. ClinicalTrials.gov. Chemotherapy plus biological therapy in treating patients with melanoma. <http://www.clinicaltrials.gov/show/NCT00006237> [accessed 09.02.2010].
  57. Tarhini AA, Shipe-Spotloe J, DeMark M, Agarwala SS, Kirkwood JM. Response to “Helping melanoma patients decide whether to choose adjuvant high-dose interferon-α2b”. Oncologist. 2006;11:538–539
  58. Gogas H, Kirkwood JM. Predictors of response to interferon therapy. Curr Opin Oncol. 2009;21:138–143
  59. Yurkovetsky ZR, Kirkwood JM, Edington HD, et al. Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b. Clin Cancer Res. 2007;13:2422–2428
  60. Tarhini AA, Stuckert J, Lee S, Sander C, Kirkwood JM. Prognostic significance of serum S100B protein in high-risk surgically resected melanoma patients participating in Intergroup Trial ECOG 1694. J Clin Oncol. 2009;27:38–44
  61. Harpio R, Einarsson R. S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma. Clin Biochem. 2004;37:512–518
  62. Gogas H, Ioannovich J, Dafni U, et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med. 2006;354:709–718
  63. Dafni U, Pectasides D, Tsoutsos D, et al. Prognostic significance of autoimmunity during adjuvant treatment of melanoma with interferon: updated follow-up. J Clin Oncol 2008;26(15s) [abstract 9024].
  64. Satzger I, Meier A, Schenck F, Kapp A, Hauschild A, Gutzmer R. Autoimmunity as a prognostic factor in melanoma patients treated with adjuvant low-dose interferon alpha. Int J Cancer. 2007;121:2562–2566
  65. Stuckert JJ, Tarhini AA, Lee S, Sander C, Kirkwood JM. Interferon alfa-induced autoimmunity and serum S100 levels as predictive and prognostic biomarkers in high-risk melanoma in the ECOG-intergroup phase II trial E2696. J Clin Oncol. 2007;25(18s):[abstract 8506]
  66. Bouwhuis MG, Suciu S, Collette S, et al. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon. J Natl Cancer Inst. 2009;101:869–877
  67. Anaya DA, Xing Y, Feng L, et al. Adjuvant high-dose interferon for cutaneous melanoma is most beneficial for patients with early stage III disease. Cancer. 2008;112:2030–2037
  68. Eggermont AM, Suciu S, Testori A, Patel P, Spatz A. EORTC Melanoma Group. Ulceration of primary melanoma and responsiveness to adjuvant interferon therapy: analysis of the adjuvant trials EORTC 18952 and EORTC 18991 in 2644 patients. J Clin Oncol. 2009;27(15s):[abstract 9007]
  69. Gogas H, Eggermont AM, Hauschild A, et al. Biomarkers in melanoma. Ann Oncol. 2009;20(Suppl. 6):vi8–vi13
  70. Mazzolini G, Murillo O, Atorrasagasti C, et al. Immunotherapy and immunoescape in colorectal cancer. World J Gastroenterol. 2007;13:5822–5831
  71. Mitchell MS, Abrams J, Thompson JA, et al. Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon alfa-2b compared with high-dose interferon alfa-2b for resected stage III cutaneous melanoma. J Clin Oncol. 2007;25:2078–2085
  72. 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;236:438–448
  73. Hsueh EC, Essner R, Foshag LJ, et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J Clin Oncol. 2002;20:4549–4554
  74. Hsueh EC, Morton DL. Antigen-based immunotherapy of melanoma: Canvaxin therapeutic polyvalent cancer vaccine. Semin Cancer Biol. 2003;13:401–407
  75. Morton DL, Mozzillo N, Thompson JF, et al. An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. J Clin Oncol. 2007;25(18s):[abstract 8508]
  76. Sondak VK, Sosman J, Unger JM, et al. Significant impact of HLA class I allele expression on outcome in melanoma patients treated with an allogeneic melanoma cell lysate vaccine. Final analysis of SWOG-9035. J Clin Oncol. 2004;22(14s):[abstract 7501]
  77. Sondak VK, Sabel MS, Mulé JJ. Allogeneic and autologous melanoma vaccines: where have we been and where are we going?. Clin Cancer Res. 2006;12:2337s–2341s
  78. de la Cruz-Merino L, Grande-Pulido E, Albero-Tamarit A, Codes-Manuel de Villena ME. Cancer and immune response: old and new evidence for future challenges. Oncologist. 2008;13:1246–1254
  79. Spitler LE, Grossbard ML, Ernstoff MS, et al. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2000;18:1614–1621
  80. Spitler LE, Weber RW, Allen RE, et al. Recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim) administered for 3years as adjuvant therapy of stages II(T4), III, and IV melanoma. J Immunother. 2009;32:632–637
  81. Perales MA, Yuan J, Powel S, et al. Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma. Mol Ther. 2008;16:2022–2029
  82. Kirkwood JM, Moschos S, Wang W. Strategies for the development of more effective adjuvant therapy of melanoma: current and future explorations of antibodies, cytokines, vaccines, and combinations. Clin Cancer Res. 2006;12:2331s–2336s
  83. Beam SL, Elias EG, Zapas JL, et al. GM-CSF & IL-2±autologous whole cell vaccine as adjuvant therapy in cutaneous melanoma: a phase II clinical trial. J Clin Oncol 2008;26(15s) [abstract 20027].
  84. ClinicalTrials.gov. Vaccine therapy and/or sargramostim in treating patients with locally advanced or metastatic melanoma. <http://www.clinicaltrials.gov/show/NCT00005034> [accessed 09.02.2010].
  85. Kruit WHJ, van Ojik HH, Brichard VG, et al. Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma. Int J Cancer. 2005;117:596–604
  86. Kruit WH, Suciu S, Dreno B, et al. Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: a randomized open-label phase II study of the EORTC Melanoma Group (16032–18031). J Clin Oncol 2008;26(15s) [abstract 9065].
  87. ClinicalTrials.gov. A phase III study to test the benefit of a new kind of anti-cancer treatment in patients with melanoma, after surgical removal of their tumor. <http://www.clinicaltrials.gov/show/NCT00796445> [accessed 09.02.2010].
  88. Molenkamp BG, van Leeuwen PA, van den Eertwegh AJ, et al. Immunomodulation of the melanoma sentinel lymph node: a novel adjuvant therapeutic option. Immunobiology. 2006;211:651–661
  89. Shu S, Cochran AJ, Huang RR, Morton DL, Maecker HT. Immune responses in the draining lymph nodes against cancer: implications for immunotherapy. Cancer Metastasis Rev. 2006;25:233–242
  90. Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol. 2009;27:83–117
  91. Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007;7:95–106
  92. O’Day SJ, Hamid O, Urba WJ. Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4). A novel strategy for the treatment of melanoma and other malignancies. Cancer. 2007;110:2614–2627
  93. Fong L, Small EJ. Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol. 2008;26:5275–5283
  94. Ribas A. Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with tremelimumab (CP-675,206). Oncologist. 2008;13(Suppl. 4):10–15
  95. Weber J. Ipilimumab: controversies in its development, utility, and autoimmune adverse events. Cancer Immunol Immunother. 2009;58:823–830
  96. Gabriel EM, Lattime EC. Anti-CTLA-4-associated antigen 4: are regulatory T cells a target?. Clin Cancer Res. 2007;13:785–788
  97. Maker AV, Phan GQ, Attia P, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12:1005–1016
  98. Berman D, Parker SM, Chasalow SD, et al. Potential biomarkers of gastrointestinal toxicities and efficacy in patients with advanced melanoma treated with ipilimumab with or without prophylactic budesonide. J Clin Oncol 2008;26(15s) [abstract 3022].
  99. Parker SM, Berman D, Bennett KL, et al. Increased humoral and cellular immunity in patients (pts) with advanced melanoma treated with ipilimumab. J Clin Oncol 2009;27(15s) [abstract 3031].
  100. Liakou CI, Kamat A, Tang DN, et al. CTLA-4 blockade increases IFNγ-producing CD4+ ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci USA. 2008;105:14987–14992
  101. Hodi FS, Butler M, Oble DA, et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA. 2008;105:3005–3010
  102. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322:271–275
  103. Ménard C, Ghiringhelli F, Roux S, et al. CTLA-4 blockade confers lymphocyte resistance to regulatory T-cells in advanced melanoma: surrogate marker of efficacy of tremelimumab?. Clin Cancer Res. 2008;14:5242–5249
  104. Ribas A, Hauschild A, Kefford R, et al. Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma. J Clin Oncol 2008;26(20s) [abstract LBA9011].
  105. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with previously treated, advanced melanoma: a randomized, double-blind, multicenter, phase 2, dose-ranging study. Lancet Oncol. 2010;11:155–164
  106. Weber J, Thompson JA, Hamid O, et al. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res. 2009;15:5591–5598
  107. O’Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety of ipilimumab monotherapy in patients with previously treated, advanced melanoma: a multicenter, single-arm, phase II study. Ann Oncol, in press.
  108. Weber J. Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with ipilimumab (MDX-010). Oncologist. 2008;13(Suppl. 4):16–25
  109. Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007;12:864–872
  110. Lin R, Yellin MJ, Lowy I, Safferman A, Chin K, Ibrahim R. An analysis of the effectiveness of specific guidelines for the management of ipilimumab-mediated diarrhea/colitis: prevention of gastrointestinal perforation and/or colectomy. J Clin Oncol 2008;26(15s) [abstract 9063].
  111. Lutzky J, Wolchok J, Hamid O, et al. Ipilimumab exerts disease control and survival benefits in advanced melanoma patients with and without immune-related adverse events (irAEs). J Clin Oncol 2009;27(15s) [abstract 9034].
  112. Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–7420
  113. ClinicalTrials.gov. Efficacy study of ipilimumab versus placebo to prevent recurrence after complete resection of high risk stage III melanoma. <http://www.clinicaltrials.gov/show/NCT00636168> [accessed 29.01.2010].
  114. Lens M. Cutaneous melanoma: interferon alpha adjuvant therapy for patients at high risk for recurrent disease. Dermatol Ther. 2006;19:9–18

PII: S0305-7372(10)00106-4

doi: 10.1016/j.ctrv.2010.06.001

Cancer Treatment Reviews
Volume 37, Issue 2 , Pages 133-142 , April 2011

Article Tools

* Image Usage & Resolution