Systematic review of medical treatment in melanoma: Current status and future prospects

Oncologist

Volumn 16, Issue 1, 2011, Pages 5-24

  Garbe, Claus ^a   Eigentler, Thomas K ^a   Keilholz, Ulrich ^b   Hauschild, Axel ^c   Kirkwood, John M ^d  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^d UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

Adjuvant treatment; BRAF inhibitors; Chemotherapy; CTLA 4; Interferon alpha; Melanoma; Vaccines

Indexed keywords

ALPHA INTERFERON; ALPHA2B INTERFERON; AMIFOSTINE; BCG VACCINE; CANCER VACCINE; CANVAXIN; CARMUSTINE; CISPLATIN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DACARBAZINE; DENDRITIC CELL VACCINE; FOTEMUSTINE; GANGLIOSIDE GM2; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 2; LEVAMISOLE; LOMEGUATRIB; OBLIMERSEN; PEGINTERFERON ALPHA2B; PEPTIDE VACCINE; PLACEBO; QS 21; RECOMBINANT ALPHA2B INTERFERON; SORAFENIB; TAMOXIFEN; TEMOZOLOMIDE; THALIDOMIDE; THYMOSIN ALPHA1; UNINDEXED DRUG; VINDESINE;

ADJUVANT THERAPY; ANTIBODY RESPONSE; CANCER ADJUVANT THERAPY; CANCER IMMUNOTHERAPY; CANCER RELAPSE; CANCER STAGING; CANCER SURVIVAL; CUTANEOUS MELANOMA; DISEASE FREE SURVIVAL; DOSAGE SCHEDULE COMPARISON; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG TOLERABILITY; DRUG WITHDRAWAL; EVENT FREE SURVIVAL; HIGH RISK PATIENT; HUMAN; LOW DRUG DOSE; LYMPH NODE METASTASIS; LYMPHADENECTOMY; MELANOMA; MULTIPLE CYCLE TREATMENT; OVERALL SURVIVAL; PRIORITY JOURNAL; REGIONAL METASTASIS; REVIEW; SYSTEMATIC REVIEW; UNSPECIFIED SIDE EFFECT;

CHEMOTHERAPY, ADJUVANT; FORECASTING; HUMANS; IMMUNOTHERAPY; MELANOMA; MOLECULAR TARGETED THERAPY; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SKIN NEOPLASMS;

EID: 79952613370     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2010-0190     Document Type: Review

References (126)

1. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004;150: 179-185.
2. Molife R, Hancock BW. Adjuvant therapy of malignant melanoma. Crit Rev Oncol Hematol 2002;44:81-102.
3. Wheatley K, Ives N, Hancock B et al. 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.
4. Mocellin S, Pasquali S, Rossi CR et al. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta analysis. J Natl Cancer Inst 2010;102:493-501.
5. 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.
6. 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.
7. Bajetta E, Del Vecchio M, Nova P et al. Multi center phase III randomized trial of poly chemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma. Ann Oncol 2006;17:571-577.
8. 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.
9. Atkins MB, Hsu J, Lee S 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.
10. Lewis KD, Robinson WA, McCarter M et al. Phase II multi center study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma. J Clin Oncol 2006;24:3157-3163.
11. Eigentler TK, Caroli UM, Radny P et al. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 2003;4:748-759.
12. Balch CM, Gershenwald JE, Soong SJ et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27:6199-6206.
13. Garbe C, Peris K, Hauschild A et al. Diagnosis and treatment of mela- noma: European consensus-based interdisciplinary guideline. Eur J Cancer 2010;46:270-283.
14. Coit DG, Andtbacka R, Bichakjian CK et al. Melanoma. J Natl Compr Canc Netw 2009;7:250-275.
15. Thomas JM, Newton-Bishop J, A'Hern R et al. Excision margins in highrisk malignant melanoma. N Engl J Med 2004;350:757-766.
16. Balch CM, Soong S, Ross MI 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.
17. Shah GD, Chapman PB. Adjuvant therapy of melanoma. Cancer J 2007; 13:217-222.
18. Fecher LA, Flaherty KT. Where are we with adjuvant therapy of stage III and IV melanoma in 2009? J Natl Compr Canc Netw 2009;7:295-304.
19. 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.
20. Creagan ET, Dalton RJ, Ahmann DL et al. Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol 1995;13:2776-2783.
21. Kirkwood JM, Ibrahim JG, Sondak VK et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of inter group trial E1690/S9111/C9190. J Clin Oncol 2000;18:2444-2458.
22. 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.
23. 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.
24. 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.
25. Cascinelli N, Belli F, MacKie RM et al. 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.
26. 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.
27. Grob JJ, Dreno B, de la SP et al. Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5mmwithout clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet 1998;351:1905-1910.
28. Eggermont AM, Gore M. Randomized adjuvant therapy trials in melanoma: surgical and systemic. Semin Oncol 2007;34:509-515.
29. 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.
30. Lens MB, Dawes M. Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 2002;20: 1818-1825.
31. Garbe C, Eigentler TK. Diagnosis and treatment of cutaneous melanoma: state of the art 2006. Melanoma Res 2007;17:117-127.
32. Wheatley K et al. Interferon-{alpha} as adjuvant therapy for melanoma: an individual patient data meta-analysis of randomised trials. J Clin Oncol 2007;25(18 suppl):Abstract 8526.
33. 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.
34. 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 randomized phase III Italian Melanoma Inter group trial. BMC Cancer 2006;6:44.
35. U.S. National Institutes of Health. Pegylated Interferon-Alpha-2a in Patients With Malignant Melanoma Stage IIA-IIIB. Available at http://clinicaltrials.gov/ct2/show/NCT00204529. Accessed June 10, 2010.
36. U.S. National Institutes of Health. PegIntron Versus IntronA in CMAJCC Stage II (EADO 2001/CMII Trial). Available at http://clinicaltrials.gov/ct2/show/NCT00221702. Accessed June 10, 2010.
37. Grob JJ et al. Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macro-metastatic nodes: EADO trial. J Clin Oncol 2010; 28(15 suppl):Abstract LBA8506.
38. 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.
39. Hauschild A, Weichenthal M, Rass K et al. Prospective randomized multi center 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.
40. Moschos SJ, Edington HD, Land SR et al. Neo adjuvant 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.
41. 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.
42. Kim CJ, Dessureault S, Gabrilovich D et al. Immunotherapy for melanoma. Cancer Control 2002;9:22-30.
43. Zarour HM, Kirkwood JM. Melanoma vaccines: early progress and future promises. Semin Cutan Med Surg 2003;22:68-75.
44. 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.
45. Isreal RJ et al. Naturally occuring and GMK-induced antibodies to GM2 in high-risk melanoma patients in study E1694/S9512/CALGB 509801. J Clin Oncol 2001;20(suppl):Abstract 1078.
46. Morton DL 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(18 suppl):Abstract 8508.
47. Eggermont A et al. Randomized phase III trial comparing postoperative adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation in stage II (T3-T4N0M0) melanoma: final results of study EORTC 18961. J Clin Oncol 2010;28(15 suppl):Abstract 8505.
48. U.S. National Institutes of Health. 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. Available at http://clinicaltrials.gov/ct2/show/NCT00796445. Accessed June 10, 2010.
49. Kirkwood JM, Lee S, Moschos SJ et al. Immunogenicity and anti tumor effects of vaccination with peptide vaccine+/-granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696. Clin Cancer Res 2009;15:1443-1451.
50. 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.
51. U.S. National Institutes of Health. Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00636168. Accessed June 10, 2010.
52. 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.
53. Middleton M, Hauschild A, Thomson D et al. Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon-{alpha}2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma. Ann Oncol 2007;18:1691-1697.
54. 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.
55. Schadendorf D, Ugurel S, Schuler-Thurner B et al. Dacarbazine (DTIC) versus vaccination with auto logous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol 2006;17: 563-570.
56. Ranson M, Hersey P, Thompson D et al. Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma. J Clin Oncol 2007;25:2540-2545.
57. Kaufmann R, Spieth K, Leiter U et al. Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. J Clin Oncol 2005;23:9001-9007.
58. Bafaloukos D, Tsoutsos D, Kalofonos H et al. Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic Cooperative Oncology Group. Ann Oncol 2005;16:950-957.
59. Danson S, Lorigan P, Arance A et al. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol 2003;21:2551-2557.
60. McDermott DF, Sosman JA, Gonzalez R et al. Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. J Clin Oncol 2008;26:2178-2185.
61. 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.
62. 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 (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol 2005;23:6747-6755.
63. Punt CJ, Suciu S, Gore MA et al. Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in patients with metastatic melanoma: a randomised phase II study of the European Organization for Research and Treatment of Cancer Melanoma Group. Eur J Cancer 2006;42:2991-2995.
64. 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.
65. 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.
66. Vuoristo MS, Hahka-Kemppinen M, Parvinen LM et al. Randomized trial of dacarbazine versus bleomycin, vincristine, lomustine and dacarbazine (BOLD) chemotherapy combined with natural or recombinant interferonalpha in patients with advanced melanoma. Melanoma Res 2005;15:291-296.
67. Reichle A, Vogt T, Coras B et al. Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 2007;17:360-364.
68. Hauschild A, Agarwala SS, Trefzer U 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.
69. Maio M, Mackiewicz A, Testori A et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol 2010;28:1780-1787.
70. Lens MB, Eisen TG. Systemic chemotherapy in the treatment of malignant melanoma. Expert Opin Pharmacother 2003;4:2205-2211.
71. Patel P et al. Extended schedule, escalated dose Temozolomide versus Dacarbazine in Stage IV malignant melanoma: Final results of the randomized phase III study (EORTC 18032). Ann Oncol 2008;19(8 suppl): Abstract LBA8.
72. Parkinson DR, Abrams JS, Wiernik PH et al. Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. J Clin Oncol 1990;8:1650-1656.
73. Agarwala S. Improving survival in patients with high-risk and metastatic melanoma: immunotherapy leads the way. Am J Clin Dermatol 2003;4: 333-346.
74. Atkins MB. Cytokine-based therapy and bio chemotherapy for advanced melanoma. Clin Cancer Res 2006;12:2353s-2358s.
75. Keilholz U, Stoter G, Punt CJ et al. Recombinant interleukin-2-based treatments for advanced melanoma: the experience of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. Cancer J Sci Am 1997;3(Suppl 1):S22-28.
76. Balmer CM. Clinical use of biologic response modifiers in cancer treatment: an overview. Part II. Colony-stimulating factors and interleukin-2. DICP 1991;25:490-498.
77. Bruton JK, Koeller JM. Recombinant interleukin-2. Pharmacotherapy 1994;14:635-656.
78. Schwartzentruber DJ et al. A phase III multi-institutional randomized study of immunization with the gp100: 209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol 2009;27(18 suppl):Abstract CRA9011.
79. U.S. National Institutes of Health. M-Vax_LowDoseInterleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT0047790. Accessed June 10, 2010.
80. U.S. National Institutes of Health. Chemotherapy With or Without Immunotherapy in Treating Patients With Stage III or Stage IV Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00003647. Accessed June 11, 2010.
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. Ives NJ, Stowe RL, Lorigan P et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol 2007;25:5426-5434.
83. O'Day SJ, Atkins MB, Boasberg P et al. Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma. J Clin Oncol 2009;27:6207-6212.
84. U.S. National Institutes of Health. Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00324155. Accessed June 11, 2010.
85. U.S. National Institutes of Health. Elesclomol (STA-4783) With Paclitaxel Versus Paclitaxel Alone in Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00522834. Accessed June 11, 2010.
86. U.S. National Institutes of Health. Trial of Dacarbazine With or Without Genasense in Advanced Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00518895. Accessed June 11, 2010.
87. Hodi FS, O'Day SJ, McDermott DF et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med 2010;363: 711-723.
88. U.S. National Institutes of Health. Carboplatin and Paclitaxel With or Without Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00110019. Accessed June 11, 2010.
89. U.S. National Institutes of Health. A Study of RO5185426 in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT01006980. Accessed June 11, 2010.
90. U.S. National Institutes of Health. A Study of Tasisulam Versus Paclitaxel as Treatment for Metastatic Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT01006252. Accessed June 11, 2010.
91. U.S. National Institutes of Health. A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00864253. Accessed June 11, 2010.
92. Ribas A 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(15 suppl):Abstract LBA9011.
93. Ribas A, Camacho LH, Lopez-Berestein G et al. Anti tumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 2005;23:8968-8977.
94. Ribas A, Hanson DC, Noe DA et al. Tremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer. The Oncologist 2007;12: 873-883.
95. Attia P, Phan GQ, Maker AV et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005;23:6043-6053.
96. 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.
97. Gomez-Navarro J et al. Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP- 675,206 in a phase I/II study. J Clin Oncol 2007;25(18 suppl): Abstract 8524.
98. Weber JS et al. The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma. J Clin Oncol 2007;25(18 suppl): Abstract 8523.
99. Kirkwood JM et al. A phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. J Clin Oncol 2008; 26(15 suppl):Abstract 9023.
100. O'Day SJ et al. Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies. J Clin Oncol 2008;26(15 suppl):Abstract 9021.
101. Hamid O et al. Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma. J Clin Oncol 2007;25(18 suppl):Abstract 8525.
102. Flaherty KT. Chemotherapy and targeted therapy combinations in advanced melanoma. Clin Cancer Res 2006;12:2366s-2370s.
103. Satyamoorthy K, Li G, Gerrero MR et al. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res 2003;63:756-759.
104. Amaravadi R et al. Updated results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma. J Clin Oncol 2007;25(18 suppl):Abstract 8527.
105. Flaherty K et al. Final results of E2603: a double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma. J Clin Oncol 2010;28(15 suppl):Abstract 8511.
106. 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.
107. Flaherty K et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol 2009;27(15 suppl):Abstract 9000.
108. McArthur G et al. Early FDG-PET responses to PLX4032 in BRAFmutant advanced melanoma. J Clin Oncol 2010;28(15 suppl):Abstract 8529.
109. U.S. National Institutes of Health. A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors. Available at http://clinicaltrials.gov/ct2/show/NCT00880321. Accessed June 11, 2010.
110. U.S. National Institutes of Health. A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00304525. Accessed June 11, 2010.
111. Kefford R et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J Clin Oncol 2010;28(15 suppl):Abstract 8503.
112. Davies BR, Logie A, McKay JS et al. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extra cellular signal regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther 2007;6:2209-2219.
113. Dummer R et al. AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: an open-label, randomized, multicenter, phase II study. J Clin Oncol 2008;26(15 suppl):Abstract 9033.
114. U.S. National Institutes of Health. Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients. Available at http://clinicaltrials.gov/ct2/show/NCT00936221. Accessed June 11, 2010.
115. Infante JR et al. Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212. J Clin Oncol 2010;28(15 Suppl):Abstract 2503.
116. Kirkwood J et al. A phase II study of tasisulam sodium (LY573636) as second-line treatment for patients with unresectable or metastatic melanoma. J Clin Oncol 2010;28(15 Suppl):Abstract 8541.
117. Dudley ME, Wunderlich JR, Shelton TE et al. Generation of tumorinfiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 2003;26:332-342.
118. Dudley ME, Yang JC, Sherry R et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 2008;26:5233-5239.
119. Dudley ME, Wunderlich JR, Yang JC et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005;23:2346-2357.
120. Besser MJ, Shapira-Frommer R, Treves AJ et al. Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother 2009;32:415-423.
121. Koike N, Pilon-Thomas S, Mule JJ. Nonmyeloablative chemotherapy followed by T-cell adoptive transfer and dendritic cell-based vaccination results in rejection of established melanoma. J Immunother 2008;31:402-412.
122. Wallen H, Thompson JA, Reilly JZ et al. Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma. PLoS One 2009;4:e4749.
123. Hauschild A et al. Phase III, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in stage IV metastatic melanoma (MM). J Clin Oncol 2009;27(18 suppl):Abstract LBA9012.
124. Bedikian AY et al. Results of pooled analyses from two phase III trials of 1,085 patients (pts) with advanced melanoma: oblimersen (OBL) plus dacarbazine (DTIC) versus DTIC alone. J Clin Oncol 2010;28(15 suppl): Abstract 8573.
125. Cancer Research, U.K. A trial looking at bevacizumab after surgery for melanoma skin cancer (AVAST-M). Available at http://www.cancerhelp.org.uk/trials/a-trial-looking-at-bevacizumab-after-surgery-for-melanomaskin-cancer. Accessed June 11, 2010.
126. U.S. National Institutes of Health. Efficacy and Safety Study of OncoVEXGM- CSF Compared to GM-CSF in Melanoma. Available at http://clinicaltrials.gov/ct2/show/NCT00769704. Accessed June 11, 2010