Clinics in Dermatology
Volume 27, Issue 6 , Pages 614-625 , November 2009

Chemotherapy and biologic therapies for melanoma: do they work?

  • Lucia B. Jilaveanu, MD, PhD

      Affiliations

    • Department of Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
  • ,
  • Saadia A. Aziz, BA

      Affiliations

    • Department of Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
  • ,
  • Harriet M. Kluger, MD

      Affiliations

    • Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street New Haven, CT 06520, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 203 785 6221; fax: +1 203 785 3788.

References 

  1. Rigel DS. Malignant melanoma: incidence issues and their effect on diagnosis and treatment in the 1990s. Mayo Clin Proc. 1997;72:367–371
  2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  3. Holman CD, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J Natl Cancer Inst. 1986;76:403–414
  4. Setlow RB, Woodhead AD, Grist E. Animal model for ultraviolet radiation-induced melanoma: platyfish-swordtail hybrid. Proc Natl Acad Sci U S A. 1989;86:8922–8926
  5. Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006;24:4738–4745
  6. Balch C, Reintgen DS, Kirkwood JM, et al. Cutaneous melanoma. In:  DeVita V,  Hellman S,  Rosenber SA editor. Cancer: principles and practice of oncology. 5th edition. Philadelphia: Lippincott-Raven; 1997;p. 1947–1994
  7. Bleehen NM, Newlands ES, Lee SM, et al. Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol. 1995;13:910–913
  8. Glover D, Ibrahim J, Kirkwood J, et al. Phase II randomized trial of cisplatin and WR-2721 versus cisplatin alone for metastatic melanoma: an Eastern Cooperative Oncology Group Study (E1686). Melanoma Res. 2003;13:619–626
  9. Evans LM, Casper ES, Rosenbluth R. Phase II trial of carboplatin in advanced malignant melanoma. Cancer Treat Rep. 1987;71:171–172
  10. Olver I, Green M, Peters W, et al. A phase II trial of zeniplatin in metastatic melanoma. Am J Clin Oncol. 1995;18:56–58
  11. Quagliana JM, Stephens RL, Baker LH, Costanzi JJ. Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study. J Clin Oncol. 1984;2:316–319
  12. Olver IN, Byrne MJ, Walpole E, et al. Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma. Eur J Cancer. 2007;43:1829–1832
  13. Jimeno A, Hitt R, Quintela-Fandino M, Cortes-Funes H. Phase II trial of vinorelbine tartrate in patients with treatment-naive metastatic melanoma. Anticancer Drugs. 2005;16:53–57
  14. Jones AL, O'Brien ME, Lorentzos A, et al. A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma. Cancer Chemother Pharmacol. 1992;30:73–76
  15. Costanza ME, Nathanson L, Schoenfeld D, et al. Results with methyl-CCNU and DTIC in metastatic melanoma. Cancer. 1977;40:1010–1015
  16. Avril MF, Aamdal S, Grob JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22:1118–1125
  17. Jacquillat C, Khayat D, Banzet P, et al. Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. Cancer. 1990;66:1873–1878
  18. Durando X, Thivat E, D'Incan M, Sinsard A, Madelmont JC, Chollet P. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives. BMC Cancer. 2005;5:147
  19. Bedikian AY, Plager C, Papadopoulos N, Eton O, Ellerhorst J, Smith T. Phase II evaluation of paclitaxel by short intravenous infusion in metastatic melanoma. Melanoma Res. 2004;14:63–66
  20. Wiernik PH, Einzig AI. Taxol in malignant melanoma. J Natl Cancer Inst Monogr. 1993;185–187
  21. Aamdal S, Wolff I, Kaplan S, et al. Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the EORTC Early Clinical Trials Group. Eur J Cancer. 1994;30A:1061–1064
  22. Newlands ES, Blackledge GR, Slack JA, et al. Phase I trial of temozolomide. (CCRG 81045: M&B 39831: NSC 362856) Br J Cancer. 1992;65:287–291
  23. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18:158–166
  24. Emmert S, Zutt M, Haenssle H, Neumann C, Kretschmer L. Inefficacy of vindesine monotherapy in advanced stage IV malignant melanoma patients previously treated with other chemotherapeutic agents. Melanoma Res. 2003;13:299–302
  25. Avril MF, Bonneterre J, Delaunay M, et al. Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group. Cancer Chemother Pharmacol. 1990;27:81–84
  26. Fletcher WS, Green S, Fletcher JR, Dana B, Jewell W, Townsend RA. Evaluation of cis-platinum and DTIC combination chemotherapy in disseminated melanoma. A Southwest Oncology Group Study. Am J Clin Oncol. 1988;11:589–593
  27. Legha SS, Ring S, Papadopoulos N, Plager C, Chawla S, Benjamin R. A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. Cancer. 1989;64:2024–2029
  28. Buzaid A, Legha SS, Winn R, et al. Cisplatin (C), vinblastine (V), and dacarbazine (D) (CVD) versus dacarbazine alone in metastatic melanoma: preliminary results of a Phase III Cancer Community Oncology Program (CCOP) trial. In: Proceedings of the American Society of Clinical Oncology. 1993;
  29. Del Prete SA, Maurer LH, O'Donnell J, Forcier RJ, LeMarbre P. Combination chemotherapy with cisplatin, carmustine, dacarbazine, and tamoxifen in metastatic melanoma. Cancer Treat Rep. 1984;68:1403–1405
  30. McClay EF, Mastrangelo MJ, Bellet RE, Berd D. Combination chemotherapy and hormonal therapy in the treatment of malignant melanoma. Cancer Treat Rep. 1987;71:465–469
  31. Lattanzi SC, Tosteson T, Chertoff J, et al. Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up. Melanoma Res. 1995;5:365–369
  32. Berd D, Mastrangelo MJ. Combination chemotherapy of metastatic melanoma. J Clin Oncol. 1995;13:796–797
  33. McClay EF, Mastrangelo MJ, Berd D, Bellet RE. Effective combination chemo/hormonal therapy for malignant melanoma: experience with three consecutive trials. Int J Cancer. 1992;50:553–556
  34. Fierro MT, Bertero M, Novelli M, et al. Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen. Melanoma Res. 1993;3:127–131
  35. Reintgen D, Saba H. Chemotherapy for stage 4 melanoma: a three-year experience with cisplatin, DTIC, BCNU, and tamoxifen. Semin Surg Oncol. 1993;9:251–255
  36. Chapman PB, Einhorn LH, Meyers ML, et al. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol. 1999;17:2745–2751
  37. Chiarion Sileni V, Nortilli R, Aversa SM, et al. Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients. Melanoma Res. 2001;11:189–196
  38. McClay EF, McClay ME. Tamoxifen: is it useful in the treatment of patients with metastatic melanoma?. J Clin Oncol. 1994;12:617–626
  39. Rusthoven JJ, Quirt IC, Iscoe NA, 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. J Clin Oncol. 1996;14:2083–2090
  40. 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
  41. Dummer R, Garbe C, Thompson JA, et al. Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma. J Clin Oncol. 2006;24:1188–1194
  42. Miller RL, Steis RG, Clark JW, et al. Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Res. 1989;49:1871–1876
  43. Creagan ET, Ahmann DL, Frytak S, Long HJ, Chang MN, Itri LM. Three consecutive phase II studies of recombinant interferon alfa-2a in advanced malignant melanoma. Updated analyses. Cancer. 1987;59(Suppl 3):638–646
  44. Robinson WA, Mughal TI, Thomas MR, Johnson M, Spiegel RJ. Treatment of metastatic malignant melanoma with recombinant interferon alpha 2. Immunobiology. 1986;172:275–282
  45. Kirkwood JM, Ibrahim J, Lawson DH, et al. High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696. J Clin Oncol. 2001;19:1430–1436
  46. 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
  47. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U. 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
  48. 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
  49. Moschos SJ, Edington HD, Land SR, et al. Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol. 2006;24:3164–3171
  50. Legha SS, Gianan MA, Plager C, Eton OE, Papadopoulous NE. Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma. Cancer. 1996;77:89–96
  51. Phan GQ, Attia P, Steinberg SM, White DE, Rosenberg SA. Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J Clin Oncol. 2001;19:3477–3482
  52. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17:2105–2116
  53. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6(Suppl 1):S11–S14
  54. Eton O, Rosenblum MG, Legha SS, et al. Phase I trial of subcutaneous recombinant human interleukin-2 in patients with metastatic melanoma. Cancer. 2002;95:127–134
  55. Karp SE. Low-dose intravenous bolus interleukin-2 with interferon-alpha therapy for metastatic melanoma and renal cell carcinoma. J Immunother. 1998;21:56–61
  56. Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst. 1993;85:622–632
  57. Rao RD, Anderson PM, Arndt CA, Wettstein PJ, Markovic SN. Aerosolized granulocyte macrophage colony-stimulating factor (GM-CSF) therapy in metastatic cancer. Am J Clin Oncol. 2003;26:493–498
  58. Robertson MJ, Mier JW, Logan T, et al. Clinical and biological effects of recombinant human interleukin-18 administered by intravenous infusion to patients with advanced cancer. Clin Cancer Res. 2006;12:4265–4273
  59. Atkins MB, Robertson MJ, Gordon M, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res. 1997;3:409–417
  60. Legha SS, Ring S, Bedikian A, et al. Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha. Ann Oncol. 1996;7:827–835
  61. Legha SS, Ring S, Eton O, Bedikian A, Plager C, Papadopoulos N. Development and results of biochemotherapy in metastatic melanoma: the University of Texas M.D. Anderson Cancer Center experience. Cancer J Sci Am. 1997;3(Suppl 1):S9–S15
  62. Flaherty LE, Atkins M, Sosman J, et al. Outpatient biochemotherapy with interleukin-2 and interferon alfa-2b in patients with metastatic malignant melanoma: results of two phase II cytokine working group trials. J Clin Oncol. 2001;19:3194–3202
  63. Ridolfi R, Chiarion-Sileni V, Guida M, et al. Cisplatin, dacarbazine with or without subcutaneous interleukin-2, and interferon alpha-2b in advanced melanoma outpatients: results from an Italian multicenter phase III randomized clinical trial. J Clin Oncol. 2002;20:1600–1607
  64. Middleton MR, Lorigan P, Owen J, et al. A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma. Br J Cancer. 2000;82:1158–1162
  65. Richtig E, Hofmann-Wellenhof R, Pehamberger H, et al. Temozolomide and interferon alpha 2b in metastatic melanoma stage IV. Br J Dermatol. 2004;151:91–98
  66. Garcia M, del Muro XG, Tres A, et al. Phase II multicentre study of temozolomide in combination with interferon alpha-2b in metastatic malignant melanoma. Melanoma Res. 2006;16:365–370
  67. Margolin KA, Doroshow JH, Akman SA, et al. Phase II trial of cisplatin and alpha-interferon in advanced malignant melanoma. J Clin Oncol. 1992;10:1574–1578
  68. Bajetta E, Di Leo A, Zampino MG, 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. J Clin Oncol. 1994;12:806–811
  69. Thomson DB, Adena M, McLeod GR, 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. Melanoma Res. 1993;3:133–138
  70. Young AM, Marsden J, Goodman A, Burton A, Dunn JA. Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma. Clin Oncol (R Coll Radiol). 2001;13:458–465
  71. Daponte A, Ascierto PA, Gravina A, et al. Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group. Cancer. 2000;89:2630–2636
  72. Bafaloukos D, Pavlidis N, Fountzilas G, et al. Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma. Am J Clin Oncol. 1996;19:296–300
  73. Feun LG, Savaraj N, Moffat F, et al. Phase II trial of recombinant interferon-alpha with BCNU, cisplatin, DTIC and tamoxifen in advanced malignant melanoma. Melanoma Res. 1995;5:273–276
  74. Stein ME, Bernstein Z, Tsalic M, et al. Chemoimmunohormonal therapy with carmustine, dacarbazine, cisplatin, tamoxifen, and interferon for metastatic melanoma: a prospective phase II study. Am J Clin Oncol. 2002;25:460–463
  75. Isacson R, Kedar E, Barak V, et al. Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response. Immunology Lett. 1992;33:127–134
  76. Dummer R, Gore ME, Hancock BW, et al. A multicenter phase II clinical trial using dacarbazine and continuous infusion interleukin-2 for metastatic melanoma. Clinical data and immunomonitoring. Cancer. 1995;75:1038–1044
  77. Flaherty LE, Robinson W, Redman BG, et al. A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma. Cancer. 1993;71:3520–3525
  78. Guida M, Latorre A, Mastria A, De Lena M. Subcutaneous recombinant interleukin-2 plus chemotherapy with cisplatin and dacarbazine in metastatic melanoma. Eur J Cancer. 1996;32A:730–733
  79. Atkins MB, O'Boyle KR, Sosman JA, et al. Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. J Clin Oncol. 1994;12:1553–1560
  80. Neri B, Vannozzi L, Fulignati C, et al. Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study. Cancer Invest. 2006;24:474–478
  81. Hauschild A, Garbe C, Stolz W, et al. Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG). Br J Cancer. 2001;84:1036–1042
  82. Khayat D, Borel C, Tourani JM, et al. Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma. J Clin Oncol. 1993;11:2173–2180
  83. Keilholz U, Goey SH, Punt CJ, et al. Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. J Clin Oncol. 1997;15:2579–2588
  84. Dorval T, Negrier S, Chevreau C, et al. Randomized trial of treatment with cisplatin and interleukin-2 either alone or in combination with interferon-alpha-2a in patients with metastatic melanoma: a Federation Nationale des Centres de Lutte Contre le Cancer Multicenter, parallel study. Cancer. 1999;85:1060–1066
  85. Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol. 1999;17:968–975
  86. Keilholz U, Punt CJ, Gore M, et al. Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2005;23:6747–6755
  87. Eton O, Legha SS, Bedikian AY, et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol. 2002;20:2045–2052
  88. Hess V, Herrmann R, Veelken H, Schwabe M. Interleukin-2-based biochemotherapy for patients with stage IV melanoma: long-term survivors outside a clinical trial setting. Oncology. 2007;73:33–40
  89. Bajetta E, Del Vecchio M, Nova P, et al. Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma. Ann Oncol. 2006;17:571–577
  90. Atkins M, Lee S, Flaherty LE, Sosman JA, Sondak VK, Kirkwood JM. A prospective randomized phase III trial of concurrent biochemotherapy (BCT) with cisplatin, vinblastine, dacarbazine (CVD), IL-2 and interferon alpha-2b (IFN) versus CVD alone in patients with metastatic melanoma (E3695): an ECOG-coordinated intergroup trial. In: Proceedings of the American Society of Clinical Oncology. Chicago, llinois. 2003;
  91. Atzpodien J, Neuber K, Kamanabrou D, et al. Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM). Br J Cancer. 2002;86:179–184
  92. Kirchner HH, Atzpodien J, Poliwoda H. Chemo-/immunotherapy in advanced malignant melanoma: carboplatin and DTIC or cisplatin, dtic, bcnu and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha-2a. Med Klin (Munich). 1996;91(Suppl 3):44–49
  93. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–954
  94. Flaherty K, Brose M, Schuchter L, et al. Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. In: Proceedings of the American Society of Clinical Oncology, New Orleans, Louisiana. 2004;
  95. Flaherty KT. Chemotherapy and targeted therapy combinations in advanced melanoma. Clin Cancer Res. 2006;12:2366s–2370s
  96. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109
  97. Karasarides M, Chiloeches A, Hayward R, et al. B-RAF is a therapeutic target in melanoma. Oncogene. 2004;23:6292–6298
  98. Eisen T, Ahmad T, Flaherty KT, et al. Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer. 2006;95:581–586
  99. Fecher LA, Amaravadi RK, Flaherty KT. The MAPK pathway in melanoma. Curr Opin Oncol. 2008;20:183–189
  100. Wyman K, Atkins MB, Prieto V, et al. Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy. Cancer. 2006;106:2005–2011
  101. Eton O, Billings L, Kim K, et al. Phase II trial of imatinib mesylate (ST-571) in metastatic melanoma (MM). In: Proceedings of the American Society of Clinical Oncology. New Orleans, Louisiana. 2004;
  102. Hodi FS, Friedlander P, Corless CL, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol. 2008;26:2046–2051
  103. Margolin K, Longmate J, Baratta T, et al. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium. Cancer. 2005;104:1045–1048
  104. Hamid O, Urba WJ, Yellin M, et al. Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma. In: Proceedings of the American Society of Clinical Oncology. Chicago, Illinois. 2007;
  105. Weber J, Hersh EM, Yellin M, et al. The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma. In: Proceedings of the American Society of Clinical Oncology. Chicago, Illinois. 2007;
  106. Downey SG, Klapper JA, Smith FO, et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007;13:6681–6688
  107. Ribas A, Antonia S, Sosman J, et al. Results of a phase II clinical trial of 2 doses and schedules off CP-675,206, an anti-CTlA4 monoclonal antibody, in patients with advanced melanoma. In: Proceedings of the American Society of Clinical Oncology. Chicago, Illinois. 2007;
  108. Wagner S, Pasenkov M, Goess G, et al. TLR9-targeted CPG immunostimulatory treatment of metastic melanoma: a phase II trial with CPG 7909 (ProMune). In: Proceedings of the American Society of Clinical Oncology. New Orleans, Louisiana. 2004;
  109. Wagner S, Weber J, Redman B, et al. CPG 7909, a TLR9 agonist immunomodulator in metastatic melanoma: a randomized phase II trial comparing two doses and in combination with DTIC. In: Proceedings of the American Society of Clinical Oncology. Orlando, Florida. 2005;
  110. Jansen B, Schlagbauer-Wadl H, Brown BD, et al. bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nat Med. 1998;4:232–234
  111. Jansen B, Wacheck V, Heere-Ress E, et al. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet. 2000;356:1728–1733
  112. Divito KA, Berger AJ, Camp RL, Dolled-Filhart M, Rimm DL, Kluger HM. Automated quantitative analysis of tissue microarrays reveals an association between high Bcl-2 expression and improved outcome in melanoma. Cancer Res. 2004;64:8773–8777
  113. Varker KA, Biber JE, Kefauver C, et al. A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma. Ann Surg Oncol. 2007;14:2367–2376
  114. Peterson AC, Swiger S, Stadler WM, Medved M, Karczmar G, Gajewski TF. Phase II study of the Flk-1 tyrosine kinase inhibitor SU5416 in advanced melanoma. Clin Cancer Res. 2004;10:4048–4054
  115. Mita MM, Rowinsky EK, Forero L, et al. A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2007;59:165–174
  116. Thomson D, Gonzalez R, Millward M, et al. A phase II trial of PI-88, a novel antiangiogenic and antimetastatic heparanase inhibitor, in patients with melanoma. In: Proceedings of the American Society of Clinical Oncology. Chicago, llinois. 2005;
  117. Grbovic OM, Basso AD, Sawai A, et al. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci U S A. 2006;103:57–62
  118. Banerji U, O'Donnell A, Scurr M, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J Clin Oncol. 2005;23:4152–4161
  119. Kefford R, Millward M, Hersey P, et al. Phase II trial of tanspimycin (KOS-953), a heat shock protein-90 (Hsp90) inhibitor in patients with metastatic melanoma. In: Proceedings of the American Society of Clinical Oncology. Chicago, llinois. 2007;

 Dr Lucia Jilaveanu is supported by the Anna Fuller Fund. Dr. Harriet Kluger is supported by National Institutes of Health Grant R0-1 CA115756-01.

PII: S0738-081X(08)00197-1

doi: 10.1016/j.clindermatol.2008.09.020

Clinics in Dermatology
Volume 27, Issue 6 , Pages 614-625 , November 2009