Seminars in Oncology
Volume 36, Issue 5 , Pages 419-431 , October 2009

Melanoma in Pediatric, Adolescent, and Young Adult Patients

  • John M. Kirkwood

      Affiliations

    • Departments of Medicine and Dermatology, University of Pittsburgh School of Medicine, and Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA
    • Corresponding Author InformationAddress correspondence to John M. Kirkwood, MD, Hillman Cancer Research Pavillion, Melanoma Program, 5117 Centre Ave, Ste L132c, Pittsburgh, PA 15213
    • ,
  • Drazen M. Jukic

      Affiliations

    • Departments of Dermatology and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
    • ,
  • Bruce J. Averbook

      Affiliations

    • Departments of Surgery and General Medical Sciences (Oncology), MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH
    • ,
  • Leonard S. Sender

      Affiliations

    • Department of Medicine, University of California, Irvine, and CHOC Children's Hospital, Orange, CA

References 

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  2. Ries L, Melbert D, Krapcho M, Stinchcomb D, Howlader N, Horner M, et al. SEER Cancer Statistics Review, 1975-2005. Bethesda, MD: National Cancer Institute; 2008;http://seer.cancer.gov/csr/1975_2005/
  3. Largent J. Cancer in California 0-39 year olds, 1988-2004, California Cancer Registry. Irvine (CA): University of California, Irvine. Unpublished data; August 2007.
  4. Cinar P, Zell JA, Taylor TH, Sender LA, Anton-Culver H. Pediatric and AYA invasive cutaneous melanoma: population-based study comparing adult melanoma cases [abstract]. J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9071
  5. Boissel N, Auclerc MF, Lhéritier V, Perel Y, Thomas X, Leblanc T, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? (Comparison of the French FRALLE-93 and LALA-94 trials). J Clin Oncol. 2003;21:774–780
  6. Bleyer A, Barr R, Hayes-Lattin B, Thomas D, Ellis C, Anderson B, et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8:288–298
  7. Bleyer A. Young adult oncology: the patients and their survival challenges. CA Cancer J Clin. 2007;57:242–255
  8. Ackerman AB, Kerl H, Sánchez J, Guo Y, Hofer A, Kelly P, et al. A clinical atlas of 101 common skin diseases: with histopathologic correlation. New York: Ardor Scribendi; 2000;
  9. Dubreuilh MW. De la mélanose circonscrite précancereuse. Ann Dermat Syph. 1912;3:129–151205-30
  10. Handley WS. The pathology of melanotic growths in relation to their operative treatment. Lancet. 1907;1:927–993
  11. Jurak L. Melanosarcoma omenti majoris et peritonei totius. Lijec Vjesn. 1917;39:171
  12. Saltykow S. Melanoma. Opca patoloska morfologija. Zagreb, Croatia: Hrvatska Državna Tiskara; 1942.
  13. Unna PG. The histopathology of the disease of the skin. Walker N, translator English ed.. New York: MacMillan; 1896;
  14. Skelton HG, Smith KJ, Holland TT, Tomaszewski MM, Lupton GP. Malignant spitz nevus. Int J Dermatol. 1992;31:639–641
  15. Smith KJ, Barrett TL, Skelton HG, Lupton GP, Graham JH. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am J Surg Pathol. 1989;13:931–939
  16. Spitz S. Melanomas of childhood. Am J Pathol. 1948;24:591–6092
  17. Elder DE, Murphy GF. Melanocytic tumors of the skin. Washington, DC: Armed Forces Institute of Pathology; 1991;
  18. Hantschke M, Bastian BC, LeBoit PE. Consumption of the epidermis: a diagnostic criterion for the differential diagnosis of melanoma and Spitz nevus. Am J Surg Pathol. 2004;28:1621–1625
  19. Cerroni L. Spitzoid tumors: a matter of perspective?. Am J Dermatopathol. 2004;26:1–3
  20. Fabrizi G, Massi G. Spitzoid malignant melanoma in teenagers: an entity with no better prognosis than that of other forms of melanoma. Histopathology. 2001;38:448–453
  21. Mooi WJ. Histopathology of Spitz naevi and “spitzoid” melanomas. Curr Top Pathol. 2001;94:65–77
  22. Walsh N, Crotty K, Palmer A, et al. Spitz nevus versus spitzoid malignant melanoma: an evaluation of the current distinguishing histopathologic criteria. Hum Pathol. 1998;29:1105–1112
  23. Barnhill RL, Argenyi ZB, From L, Glass LF, Maize JC, Mihm MC, et al. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol. 1999;30:513–520
  24. Busam KJ, Pulitzer M. Sentinel lymph node biopsy for patients with diagnostically controversial spitzoid melanocytic tumors?. Adv Anat Pathol. 2008;15:253–262
  25. Gamblin TC, Edington H, Kirkwood JM, Rao UN. Sentinel lymph node biopsy for atypical melanocytic lesions with spitzoid features. Ann Surg Oncol. 2006;13:1664–1670
  26. Lohmann CM, Coit DG, Brady MS, Berwick M, Busam KJ. Sentinel lymph node biopsy in patients with diagnostically controversial spitzoid melanocytic tumors. Am J Surg Pathol. 2002;26:47–55
  27. Murali R, Sharma RN, Thompson JF, Stretch JR, Lee CS, McCarthy SW, et al. Sentinel lymph node biopsy in histologically ambiguous melanocytic tumors with spitzoid features (so-called atypical spitzoid tumors). Ann Surg Oncol. 2008;15:302–309
  28. Su LD, Fullen DR, Sondak VK, Johnson TM, Lowe L. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer. 2003;97:499–507
  29. Urso C, Borgognoni L, Saieva C, Ferrara G, Tinacci G, Begliomini B, et al. Sentinel lymph node biopsy in patients with “atypical Spitz tumors.” (A report on 12 cases). Hum Pathol. 2006;37:816–823
  30. Ionescu DN, Arida M, Jukic DM. Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation. Arch Pathol Lab Med. 2006;130:45–51
  31. Bastian BC. Molecular genetics of melanocytic neoplasia: practical applications for diagnosis. Pathology. 2004;36:458–461
  32. Bauer J, Bastian BC. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther. 2006;19:40–49
  33. Palmedo G, Hantschke M, Rütten A, Mentzel T, Hügel H, Flaig MJ, et al. The T1796A mutation of the BRAF gene is absent in Spitz nevi. J Cutan Pathol. 2004;31:266–270
  34. Yazdi AS, Palmedo G, Flaig MJ, Puchta U, Reckwerth A, Rütten A, et al. Mutations of the BRAF gene in benign and malignant melanocytic lesions. J Invest Dermatol. 2003;121:1160–1162
  35. Gill M, Cohen J, Renwick N, et al. Genetic similarities between Spitz nevus and spitzoid melanoma in children. Cancer. 2004;101:2636–2640
  36. Fullen DR, Poynter JN, Lowe L, Su LD, Elder JT, Nair RP, et al. BRAF and NRAS mutations in spitzoid melanocytic lesions. Mod Pathol. 2006;19:1324–1332
  37. Poynter JN, Elder JT, Fullen DR, Nair RP, Soengas MS, Johnson TM, et al. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006;16:267–273
  38. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622–3634
  39. Ross MI, Balch CM, Cascinelli N, et al. Excision of primary melanoma. In:  Balch C,  Houghton A,  Sober A, et al. editor. Cutaneous melanoma. 4th ed.. St. Louis, MO: Quality Medical Publishing; 2003;p. 209–230
  40. Kesmodel SB, Karakousis GC, Botbyl JD, Canter RJ, Lewis RT, Wahl PM, et al. Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas. Ann Surg Oncol. 2005;12:449–458
  41. Sondak VK, Taylor JM, Sabel MS, Wang Y, Lowe L, Grover AC, et al. Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol. 2004;11:247–258
  42. Balch CM, Gershenwald JE, Soong S-j, Sober AJ, Kirkwood JM. Melanoma staging and classification. In:  Balch CM,  Houghton AN,  Sober AJ, et al. editor. Cutaneous melanoma. 5th ed.. St. Louis: Quality Medical Publishing; 2009;p. 65–86
  43. Chao C, Martin RC, Ross MI, Reintgen DS, Edwards MJ, Noyes RD, et al. Correlation between prognostic factors and increasing age in melanoma. Ann Surg Oncol. 2004;11:259–264
  44. Karakousis GC, Gimotty PA, Botbyl JD, Kesmodel SB, Elder DE, Elenitsas R, et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol. 2006;13:533–541
  45. White R, Stell V, Soong S, Dickerson M, Pockaj B, Avisar E, et al. Factors predictive of sentinel and non-sentinel lymph node positivity in melanoma from a large multicenter database. Ann Surg Oncol. 2008;15:16
  46. Hamre MR, Chuba P, Bakhshi S, Thomas R, Severson RK. Cutaneous melanoma in childhood and adolescence. Pediatr Hematol Oncol. 2002;19:309–317
  47. Pappo A, Ries L, Herzog C, Bleyer A. Malignant melanoma in the first three decades of life: a report from the U.S. Surveillance, Epidemiology and End Results (SEER) program [abstract]. J Clin Oncol (ASCO Meeting Abstracts). 2004;22:7557
  48. Strouse JJ, Fears TR, Tucker MA, Wayne AS. Pediatric melanoma: risk factor and survival analysis of the Surveillance, Epidemiology and End Results database. J Clin Oncol. 2005;23:4735–4741
  49. Ferrari A, Bono A, Baldi M, Collini P, Casanova M, Pennacchioli E, et al. Does melanoma behave differently in younger children than in adults? (A retrospective study of 33 cases of childhood melanoma from a single institution). Pediatrics. 2005;115:649–654
  50. Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM. Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol. 2007;25:1363–1368
  51. Roaten JB, Partrick DA, Pearlman N, Gonzalez RJ, Gonzalez R, McCarter MD. Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents. J Pediatr Surg. 2005;40:232–235
  52. Roaten JB, Partrick DA, Bensard D, Pearlman N, Gonzalez R, Fitzpatrick J, et al. Survival in sentinel lymph node-positive pediatric melanoma. J Pediatr Surg. 2005;40:988–992
  53. Livestro DP, Kaine EM, Michaelson JS, Mihm MC, Haluska FG, Muzikansky A, et al. Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer. 2007;110:614–624
  54. Bütter A, Hui T, Chapdelaine J, Beaunoyer M, Flageole H, Bouchard S. Melanoma in children and the use of sentinel lymph node biopsy. J Pediatr Surg. 2005;40:797–800
  55. Toro J, Ranieri JM, Havlik RJ, Coleman JJ, Wagner JD. Sentinel lymph node biopsy in children and adolescents with malignant melanoma. J Pediatr Surg. 2003;38:1063–1065
  56. Balch CM, Soong S, Ross MI, Urist MM, Karakousis CP, Temple WJ, et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm) (Intergroup Melanoma Surgical Trial). Ann Surg Oncol. 2000;7:87–97
  57. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–1317
  58. Gimotty P, Yoon F, Hammond R, Rosenbaum P, Guerry D. Sentinel lymph node biopsy (SLNB) improves survival among SEER patients with melanoma. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9005
  59. Mones JM, Ackerman AB. “Atypical” Spitz's nevus, “malignant” Spitz's nevus, and “metastasizing” Spitz's nevus: a critique in historical perspective of three concepts flawed fatally. Am J Dermatopathol. 2004;26:310–333
  60. Kwon EJ, Winfield HL, Rosenberg AS. The controversy and dilemma of using sentinel lymph node biopsy for diagnostically difficult melanocytic proliferations. J Cutan Pathol. 2008;35:1075–1077
  61. Biddle DA, Evans HL, Kemp BL, El-Naggar AK, Harvell JD, White WL, et al. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol. 2003;27:673–681
  62. Brennick JB, Yan S. False-positive cells in sentinel lymph nodes. Semin Diagn Pathol. 2008;25:116–119
  63. Carson KF, Wen DR, Li PX, Lana AM, Bailly C, Morton DL, et al. Nodal nevi and cutaneous melanomas. Am J Surg Pathol. 1996;20:834–840
  64. Fisher CJ, Hill S, Millis RR. Benign lymph node inclusions mimicking metastatic carcinoma. J Clin Pathol. 1994;47:245–247
  65. LeBoit PE. What do these cells prove?. Am J Dermatopathol. 2003;25:355–356
  66. Mooi WJ, Krausz T. Spitz nevus versus spitzoid melanoma: diagnostic difficulties, conceptual controversies. Adv Anat Pathol. 2006;13:147–156
  67. Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003;163:1765–1770
  68. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135–2147
  69. Harvell JD, Kohler S, Zhu S, Hernandez-Boussard T, Pollack JR, van de Rijn M. High-resolution array-based comparative genomic hybridization for distinguishing paraffin-embedded Spitz nevi and melanomas. Diagn Mol Pathol. 2004;13:22–25
  70. Kayton ML, La Quaglia MP. Sentinel node biopsy for melanocytic tumors in children. Semin Diagn Pathol. 2008;25:95–99
  71. Wright BE, Scheri RP, Ye X, Faries MB, Turner RR, Essner R, et al. Importance of sentinel lymph node biopsy in patients with thin melanoma. Arch Surg. 2008;143:892–899
  72. Haddad FF, Stall A, Messina J, Brobeil A, Ramnath E, Glass LF, et al. The progression of melanoma nodal metastasis is dependent on tumor thickness of the primary lesion. Ann Surg Oncol. 1999;6:144–149
  73. Joseph E, Brobeil A, Glass F, Glass J, Messina J, DeConti R, et al. Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes. Ann Surg Oncol. 1998;5:119–125
  74. 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
  75. 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
  76. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS, 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
  77. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, 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
  78. 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
  79. Hancock BW, Wheatley K, Harris S, Ives N, Harrison G, Horsman JM, 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
  80. Moschos SJ, Kirkwood JM, Konstantinopoulos PA. Present status and future prospects for adjuvant therapy of melanoma: time to build upon the foundation of high-dose interferon alfa-2b. J Clin Oncol. 2004;22:11–14
  81. Cole BF, Gelber RD, Kirkwood JM, Goldhirsch A, Barylak E, Borden E. 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
  82. Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. 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
  83. Wheatley K, Ives N, Eggermont A, Kirkwood J, Cascinelli N, Markovic SN, et al. Interferon-α as adjuvant therapy for melanoma: an individual patient data meta-analysis of randomised trials. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;25:8526
  84. Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med. 2006;354:709–718
  85. Kirkwood JM, Farkas DL, Chakraborty A, Dyer KF, Tweardy DJ, Abernethy JL, et al. Systemic interferon-α (IFN-α) treatment leads to Stat3 inactivation in melanoma precursor lesions. Mol Med. 1999;5:11–20
  86. Tatsumi T, Kierstead LS, Ranieri E, et al. Disease-associated bias in T helper type 1 (Th1)/Th2 CD4+ T cell responses against MAGE-6 in HLA-DRB*10401+ patients with renal cell carcinoma or melanoma. J Exp Med. 2002;196:619–628
  87. Pectasides D, Dafni U, Bafaloukos D, Skarlos D, Polyzos A, Tsoutsos 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
  88. Critchley-Thorne RJ, Yan N, Nacu S, Weber J, Holmes SP, Lee PP. Down-regulation of the interferon signaling pathway in T lymphocytes from patients with metastatic melanoma. PLoS Med. 2007;4:e176
  89. Moschos SJ, Edington HD, Land SR, Rao UN, Jukic D, Shipe-Spotloe J, 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
  90. Eggermont AM, Suciu S, MacKie R, Ruka W, Testori A, Kruit W, 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
  91. Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, 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
  92. 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
  93. Mohr P, Hauschild A, Enk A, Trefzer U, Rass K, Grabbe S, 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. U. (NCT00226408) [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9040
  94. Anaya DA, Xing Y, Feng L, Huang X, Camacho LH, Ross MI, et al. Adjuvant high-dose interferon for cutaneous melanoma is most beneficial for patients with early stage III disease. Cancer. 2008;112:2030–2037
  95. Navid F, Furman WL, Fleming M, Rao BN, Kovach S, Billups CA, et al. The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer. 2005;103:780–787
  96. Eggermont AM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?. Eur J Cancer. 2004;40:1825–1836
  97. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, 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
  98. Patel PM, Suciu S, Mortier L, Kruit W, Robert C, Schadendorf D, et al. Extended schedule, escalated dose temozlomide versus dacarbazine in stage IV malignant melanoma: final results of the randomised phase III study (EORTC 18032). [abstract] Annals of Oncology (ESMO Meeting Abstracts). 2008;19:LBA8
  99. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, 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
  100. 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
  101. Eton O, Legha SS, Bedikian AY, Lee JJ, Buzaid AC, Hodges C, et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol. 2002;20:2045–2052
  102. Atkins MB, Hsu J, Lee S, Cohen GI, Flaherty LE, Sosman JA, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2008;26:5748–5754
  103. Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, 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
  104. Weber JS, Berman D, Siegel J, Minor D, Amin AT, Ron I, et al. Safety and efficacy of ipilimumab with or without prophylactic budesonide in treatment-naive and previously treated patients with advanced melanoma. J.A. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9010
  105. Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008;26:5950–5956
  106. Hamid O, Chin K, Li J, Neyns B, Linette G, Negrier S, et al. Dose effect of ipilimumab in patients with advanced melanoma: results from a phase II, randomized, dose-ranging study [abstract]. J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9025
  107. Kirkwood JM, Lorigan P, Hersey P, Hauschild A, Robert C, McDermott DF, et al. A phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9023
  108. Ribas A, Hauschild A, Kefford R, Punt CJ, Haanen JB, Marmol M, 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. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:LBA9011
  109. Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27:2823–2830
  110. Kim KB, Saro J, Moschos SS, Hwu P, Tarhini AA, Hwu W, et al. A phase I dose finding and biomarker study of TKI258 (dovitinib lactate) in patients with advanced melanoma. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9026
  111. Flaherty K, Puzanov I, Sosman J, Kim K, Ribas A, McArthur G, et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. [abstract] J Clin Oncol (ASCO Meeting Abstracts). 2009;27:9000

 Funded by NIH SPORE in Skin Cancer Grant No. P50 CA121973-02, and supported by the Clinical and Translational Science Institute and the Grant Channell Foundation.

PII: S0093-7754(09)00136-5

doi: 10.1053/j.seminoncol.2009.07.001

Seminars in Oncology
Volume 36, Issue 5 , Pages 419-431 , October 2009

Article Tools