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Journal of Skin Cancer
Volume 2013 (2013), Article ID 735282, 10 pages
http://dx.doi.org/10.1155/2013/735282
Review Article

Latest Approved Therapies for Metastatic Melanoma: What Comes Next?

Department of Oncology, Stem Cells and Nanomedicine, Fluorotronics, Inc., 2453 Cades Way, Building C, San Diego, CA 92081, USA

Received 10 August 2012; Revised 16 January 2013; Accepted 18 January 2013

Academic Editor: M. Lebwohl

Copyright © 2013 Farid Menaa. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. T. DeVita, T. S. Lawrence, and S. A. Rosenberg, DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 8th edition, 2008.
  2. A. Jemal, R. Siegel, J. Xu, and E. Ward, “Cancer statistics, 2010,” CA: Cancer Journal for Clinicians, vol. 60, no. 5, pp. 277–300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. N. Howlader, L. A. G. Ries, A. B. Mariotto, M. E. Reichman, J. Ruhl, and K. A. Cronin, “Improved estimates of cancer-specific survival rates from population-based data,” Journal of the National Cancer Institute, vol. 102, no. 20, pp. 1584–1598, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Bestak and G. M. Halliday, “Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice,” Photochemistry and Photobiology, vol. 64, no. 6, pp. 969–974, 1996. View at Scopus
  5. F. G. Haluska and F. S. Hodi, “Molecular genetics of familial cutaneous melanoma,” Journal of Clinical Oncology, vol. 16, no. 2, pp. 670–682, 1998. View at Scopus
  6. K. H. Kraemer, M. M. Lee, A. D. Andrews, and W. C. Lambert, “The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer: the xeroderma pigmentosum paradigm,” Archives of Dermatology, vol. 130, no. 8, pp. 1018–1021, 1994. View at Publisher · View at Google Scholar · View at Scopus
  7. G. J. Hill, E. T. Krementz, and H. Z. Hill, “Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy (Central Oncology Group Protocols 7130, 7131, and 7131A),” Cancer, vol. 53, no. 6, pp. 1299–1305, 1984. View at Scopus
  8. M. B. Atkins, M. T. Lotze, J. P. Dutcher et al., “High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993,” Journal of Clinical Oncology, vol. 17, no. 7, pp. 2105–2116, 1999. View at Scopus
  9. G. Q. Phan, P. Attia, S. M. Steinberg, D. E. White, and S. A. Rosenberg, “Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma,” Journal of Clinical Oncology, vol. 19, no. 15, pp. 3477–3482, 2001. View at Scopus
  10. P. B. Chapman, A. Hauschild, C. Robert et al., “Improved survival with vemurafenib in melanoma with BRAF V600E mutation,” The The New England Journal of Medicine, vol. 364, no. 26, pp. 2507–2516, 2011. View at Publisher · View at Google Scholar
  11. F. S. Hodi, S. J. O'Day, D. F. McDermott et al., “Improved survival with ipilimumab in patients with metastatic melanoma,” The New England Journal of Medicine, vol. 363, no. 8, pp. 711–723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Carrat, F. Bani-Sadr, S. Pol et al., “Pegylated interferon alfa-2b versus standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial,” The Journal of the American Medical Association, vol. 292, no. 23, pp. 2839–2848, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. A. M. Eggermont, S. Suciu, M. Santinami 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,” The Lancet, vol. 372, no. 9633, pp. 117–126, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. K. T. Flaherty, I. Puzanov, K. B. Kim et al., “Inhibition of mutated, activated BRAF in metastatic melanoma,” The New England Journal of Medicine, vol. 363, no. 9, pp. 809–819, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. K. S. M. Smalley and V. K. Sondak, “Melanoma—an unlikely poster child for personalized cancer therapy,” The New England Journal of Medicine, vol. 363, no. 9, pp. 876–878, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Ribas, K. Kim, L. Schuchter, R. Gonzalez, et al., “BRIM-2: an open label, multicenter phase II study of vemurafenib in previously treated patients with BRAF V600E mutation-positive metastatic melanoma,” Journal of Clinical Oncology, vol. 29, abstract no. 8509, 2011.
  17. L. Si, Y. Kong, X. Xu et al., “Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort,” European Journal of Cancer, vol. 48, no. 1, pp. 94–100, 2012.
  18. A. M. Menzies, L. Visintin, M. D. Chatfield et al., “Long. BRAF mutation by age-decade and body mass index in metastatic melanoma,” Journal of Clinical Oncology, vol. 29, abstract no. 8507, 2011.
  19. I. Melero, S. Hervas-Stubbs, M. Glennie, D. M. Pardoll, and L. Chen, “Immunostimulatory monoclonal antibodies for cancer therapy,” Nature Reviews Cancer, vol. 7, no. 2, pp. 95–106, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Robert, L. Thomas, I. Bondarenko et al., “Ipilimumab plus dacarbazine for previously untreated metastatic melanoma,” The New England Journal of Medicine, vol. 364, no. 26, pp. 2517–2526, 2011. View at Publisher · View at Google Scholar
  21. J. D. Wolchok, L. Thomas, I. N. Bondarenko et al., “Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients with unresectable stage III or IV melanoma,” Journal of Clinical Oncology, vol. 29, abstract no. LBA5, 2011.
  22. B. F. Cole, R. D. Gelber, J. M. Kirkwood, A. Goldhirsch, E. Barylak, and E. Borden, “Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern cooperative oncology group study,” Journal of Clinical Oncology, vol. 14, no. 10, pp. 2666–2673, 1996. View at Scopus
  23. A. M. Eggermont, S. Suciu, M. Santinami et al., “EORTC, 18991 phase III trial: long-term adjuvant pegylated interferon-α2b (PEG-IFN) versus observation in resected stage III melanoma: long-term results at 7. 6-years follow-up,” Journal of Clinical Oncology, vol. 29, no. 15, abstract no. 8506b, 2011.
  24. W. J. Hwu, K. S. Panageas, J. H. Menell et al., “Phase II study of temozolomide plus pegylated interferon-α-2b for metastatic melanoma,” Cancer, vol. 106, no. 11, pp. 2445–2451, 2006. View at Publisher · View at Google Scholar
  25. L. E. Flaherty, J. Moon, M. B. Atkins et al., “Phase III trial of high-dose interferon α-2b versus cisplatin, vinblastine, DTIC plus IL-2 and interferon in patients with high-risk melanoma (SWOG S0008): an Intergroup study of CALGB, COC, ECOG and SWOG,” Journal of Clinical Oncology, vol. 30, abstract no. 8504, 2012.
  26. H. Davies, G. R. Bignell, C. Cox et al., “Mutations of the BRAF gene in human cancer,” Nature, vol. 417, no. 6892, pp. 949–954, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. J. A. Curtin, J. Fridlyand, T. Kageshita et al., “Distinct sets of genetic alterations in melanoma,” The New England Journal of Medicine, vol. 353, no. 20, pp. 2135–2147, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. J. A. Jakob, R. L. Bassett, C. S. Ng et al., “Clinical characteristics and outcomes associated with BRAF and NRAS mutations in metastatic melanoma,” Cancer, vol. 118, no. 16, pp. 4014–4023, 2011.
  29. N. Dhomen and R. Marais, “BRAF signaling and targeted therapies in melanoma,” Hematology/Oncology Clinics of North America, vol. 23, no. 3, pp. 529–545, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. G. S. Inamdar, S. V. Madhunapantula, and G. P. Robertson, “Targeting the MAPK pathway in melanoma: why some approaches succeed and other fail,” Biochemical Pharmacology, vol. 80, no. 5, pp. 624–637, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. S. M. Wilhelm, C. Carter, L. Tang 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 Research, vol. 64, no. 19, pp. 7099–7109, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Eisen, T. Ahmad, K. T. Flaherty et al., “Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis,” British Journal of Cancer, vol. 95, no. 5, pp. 581–586, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. D. F. McDermott, J. A. Sosman, R. Gonzalez 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,” Journal of Clinical Oncology, vol. 26, no. 13, pp. 2178–2185, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Hauschild, S. S. Agarwala, U. Trefzer 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,” Journal of Clinical Oncology, vol. 27, no. 17, pp. 2823–2830, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Kefford, H. Arkenau, M. Brown, M. Millward, 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,” Journal of Clinical Oncology, vol. 28, abstract no. 8503, 2010.
  36. R. Dummer, J. Rinderknecht, S. M. Goldinger et al., “An open-label pilot study of vemurafenib in previously treated metastatic melanoma patients with brain metastases,” Journal of Clinical Oncology, vol. 29, abstract no. 8548, 2011.
  37. F. Su, A. Viros, C. Milagre et al., “RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors,” The New England Journal of Medicine, vol. 366, no. 3, pp. 207–215, 2012. View at Publisher · View at Google Scholar
  38. E. Y. Chu, K. A. Wanat, C. J. Miller et al., “Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study,” Journal of the American Academy of Dermatology, vol. 67, no. 6, pp. 1265–1272, 2012. View at Publisher · View at Google Scholar
  39. P. A. Oberholzer, D. Kee, P. Dziunycz et al., “RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors,” Journal of Clinical Oncology, vol. 30, no. 3, pp. 316–321, 2012. View at Publisher · View at Google Scholar
  40. M. E. Lacouture, K. O'Reilly, N. Rosen, and D. B. Solit, “Induction of cutaneous squamous cell carcinomas by RAF inhibitors: cause for concern?” Journal of Clinical Oncology, vol. 30, no. 3, pp. 329–330, 2012. View at Publisher · View at Google Scholar
  41. N. Wagle, C. Emery, M. F. Berger et al., “Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling,” Journal of Clinical Oncology, vol. 29, no. 22, pp. 3085–3096, 2011. View at Publisher · View at Google Scholar
  42. M. E. Gorre, M. Mohammed, K. Ellwood et al., “Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification,” Science, vol. 293, no. 5531, pp. 876–880, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. L. M. Ellis and D. J. Hicklin, “Resistance to targeted therapies: refining anticancer therapy in the era of molecular oncology,” Clinical Cancer Research, vol. 15, no. 24, pp. 7471–7478, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Nazarian, H. Shi, Q. Wang et al., “Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation,” Nature, vol. 468, no. 7326, pp. 973–977, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. C. M. Johannessen, J. S. Boehm, S. Y. Kim et al., “COT drives resistance to RAF inhibition through MAP kinase pathway reactivation,” Nature, vol. 468, no. 7326, pp. 968–972, 2010. View at Publisher · View at Google Scholar
  46. J. Villanueva, A. Vultur, J. T. Lee et al., “Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K,” Cancer Cell, vol. 18, no. 6, pp. 683–695, 2010. View at Publisher · View at Google Scholar
  47. C. M. Emery, K. G. Vijayendran, M. C. Zipser et al., “MEK1 mutations confer resistance to MEK and B-RAF inhibition,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 48, pp. 20411–20416, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Montagut, S. V. Sharma, T. Shioda et al., “Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma,” Cancer Research, vol. 68, no. 12, pp. 4853–4861, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Guix, A. C. Faber, S. E. Wang et al., “Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins,” Journal of Clinical Investigation, vol. 118, no. 7, pp. 2609–2619, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. R. D. Carvajal, C. R. Antonescu, J. D. Wolchok et al., “KIT as a therapeutic target in metastatic melanoma,” The Journal of the American Medical Association, vol. 305, no. 22, pp. 2327–2334, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. K. H. T. Paraiso, Y. Xiang, V. W. Rebecca et al., “PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression,” Cancer Research, vol. 71, no. 7, pp. 2750–2760, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Robert, K. T. Flaherty, P. Hersey et al., “METRIC phase III study: efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM),” Journal of Clinical Oncology, vol. 30, no. 18, absrtact no. LBA8509, 2012.
  53. Clinical trials investigating c-KIT inhibitors for advanced melanomahttp://www.clinicaltrials.gov/ct2/results?term=cKIT+inhibitors&cond=%22Melanoma%22.
  54. H. M. Kluger, A. Z. Dudek, C. McCann et al., “A phase 2 trial of dasatinib in advanced melanoma,” Cancer, vol. 117, no. 10, pp. 2202–2208, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. S. E. Woodman, J. C. Trent, K. Stemke-Hale et al., “Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates,” Molecular Cancer Therapeutics, vol. 8, no. 8, pp. 2079–2085, 2009. View at Publisher · View at Google Scholar
  56. J. A. Curtin, K. Busam, D. Pinkel, and B. C. Bastian, “Somatic activation of KIT in distinct subtypes of melanoma,” Journal of Clinical Oncology, vol. 24, no. 26, pp. 4340–4346, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Kitayama, Y. Kanakura, T. Furitsu et al., “Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines,” Blood, vol. 85, no. 3, pp. 790–798, 1995. View at Scopus
  58. K. B. Kim, O. Eton, D. W. Davis et al., “Phase II trial of imatinib mesylate in patients with metastatic melanoma,” British Journal of Cancer, vol. 99, no. 5, pp. 734–740, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Guo, L. Si, Y. Kong et al., “Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification,” Journal of Clinical Oncology, vol. 29, no. 21, pp. 2904–2909, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. “Clinical trials investigating vemurafenib plus ipilimumab for advanced melanoma,” http://www.clinicaltrials.gov/ct2/show/NCT01400451?term=vemurafenib&cond=%22Melanoma%22&rank=21.
  61. G. V. Long, U. Trefzer, M. A. Davies et al., “Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial,” The Lancet Oncology, vol. 13, no. 11, pp. 1087–1095, 2012. View at Publisher · View at Google Scholar
  62. J. M. Kirkwood, G. V. Long, U. Trefzer et al., “BREAK-MB: a phase II study assessing overall intracranial response rate to dabrafenib (GSK2118436) in patients with BRAF V600E/k mutation-positive melanoma with brain metastases,” Journal of Clinical Oncology, vol. 30, abstract no. 8501, 2012.
  63. A. Hauschild, J. J. Grob, L. V. Demidov, et al., “Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma,” Journal of Clinical Oncology, vol. 30, abstract no. LBA8500, 2012.
  64. J. R. Infante, G. S. Falchook, D. P. Lawrence, J. S. Weber, et al., “Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 dosed in combination with oral BRAF inhibitor,” Journal of Clinical Oncology, vol. 29, abstract no. CRA8503, 2011.
  65. J. S. Weber, K. T. Flaherty, J. R. Infante, et al., “Updated safety and efficacy results from a phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naive metastatic melanoma,” Journal of Clinical Oncology, vol. 30, abstract no. 8510, 2012.
  66. K. T. Flaherty, J. R. Infante, A. Daud et al., “Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations,” The New England Journal of Medicine, vol. 367, no. 18, pp. 1694–1703, 2012. View at Publisher · View at Google Scholar
  67. S. Wee, Z. Jagani, K. X. Xiang et al., “PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers,” Cancer Research, vol. 69, no. 10, pp. 4286–4293, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. E. Halilovic, Q. B. She, Q. Ye et al., “PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling,” Cancer Research, vol. 70, no. 17, pp. 6804–6814, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. M. E. Keir, M. J. Butte, G. J. Freeman, and A. H. Sharpe, “PD-1 and its ligands in tolerance and immunity,” Annual Review of Immunology, vol. 26, pp. 677–704, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. J. L. Riley, “PD-1 signaling in primary T cells,” Immunological Reviews, vol. 229, no. 1, pp. 114–125, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Okazaki and T. Honjo, “The PD-1-PD-L pathway in immunological tolerance,” Trends in Immunology, vol. 27, no. 4, pp. 195–201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. J. R. Brahmer, C. G. Drake, I. Wollner et al., “Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates,” Journal of Clinical Oncology, vol. 28, no. 19, pp. 3167–3175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. F. S. Hodi, M. Sznol, D. F. McDermott, et al., “Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma,” Journal of Clinical Oncology, vol. 20, abstract no. 8507, 2012.
  74. K. B. Kim, J. A. Sosman, J. P. Fruehauf et al., “BEAM: a randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma,” Journal of Clinical Oncology, vol. 30, no. 1, pp. 34–41, 2012. View at Publisher · View at Google Scholar
  75. A. Sandler, R. Gray, M. C. Perry et al., “Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer,” The New England Journal of Medicine, vol. 355, no. 24, pp. 2542–2550, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. F. S. Hodi, P. A. Friedlander, M. B. Atkins et al., “A phase I trial of ipilimumab plus bevacizumab in patients with unresectable stage III or stage IV melanoma,” Journal of Clinical Oncology, vol. 29, abstract no. 8511, 2011.
  77. S. N. Markovic, V. J. Suman, W. K. Nevala et al., “A dose-escalation study of aerosolized sargramostim in the treatment of metastatic melanoma: an NCCTG study,” American Journal of Clinical Oncology, vol. 31, no. 6, pp. 573–579, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. L. E. Spitler, R. W. Weber, R. E. Allen et al., “Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) administered for 3 years as adjuvant therapy of stages II(T4), III, and IV melanoma,” Journal of Immunotherapy, vol. 32, no. 6, pp. 632–637, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. “Ipilimumab with or without sargramostim in treating patients with stage III or stage IV melanoma that cannot be removed by surgery,” http://clinicaltrials.gov/show/NCT01134614.
  80. D. Khayat, B. Giroux, J. Berille et al., “Fotemustine in the treatment of brain primary tumors and metastases,” Cancer Investigation, vol. 12, no. 4, pp. 414–420, 1994. View at Scopus
  81. M. F. Avril, S. Aamdal, J. J. Grob et al., “Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study,” Journal of Clinical Oncology, vol. 22, no. 6, pp. 1118–1125, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. A. M. Di Giacomo, P. A. Ascierto, L. Pilla et al., “Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial,” The Lancet Oncology, vol. 13, no. 9, pp. 879–886, 2012. View at Publisher · View at Google Scholar
  83. F. Menaa and B. Menaa, “Development of mitotane lipid nanocarriers and enantiomers: two-in-one solution to efficiently treat adreno-cortical carcinoma,” Current Medicinal Chemistry, vol. 19, no. 34, pp. 5854–5862, 2012. View at Publisher · View at Google Scholar
  84. H. L. McArthur, H. Rugo, B. Nulsen et al., “A feasibility study of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer,” Clinical Cancer Research, vol. 17, no. 10, pp. 3398–3407, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Abrishami, S. Zarei-Ghanavati, D. Soroush, M. Rouhbakhsh, M. R. Jaafari, and B. Malaekeh-Nikouei, “Preparation, characterization, and in vivo evaluation of nanoliposomes-encapsulated bevacizumab (avastin) for intravitreal administration,” Retina, vol. 29, no. 5, pp. 699–703, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. S. A. Rosenberg, B. S. Packard, P. M. Aebersold et al., “Use of tumor-infiltrating lymphocyts and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report,” The New England Journal of Medicine, vol. 319, no. 25, pp. 1676–1680, 1988. View at Scopus
  87. S. A. Rosenberg, J. R. Yannelli, J. C. Yang et al., “Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2,” Journal of the National Cancer Institute, vol. 86, no. 15, pp. 1159–1166, 1994. View at Scopus
  88. S. A. Rosenberg and M. E. Dudley, “Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 2, pp. 14639–14645, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. M. E. Dudley, J. R. Wunderlich, J. C. Yang et al., “Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma,” Journal of Clinical Oncology, vol. 23, no. 10, pp. 2346–2357, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. S. A. Rosenberg, J. C. Yang, R. M. Sherry et al., “Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy,” Clinical Cancer Research, vol. 17, no. 13, pp. 4550–4557, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. M. E. Dudley, “Adoptive cell therapy for patients with melanoma,” Journal of Cancer, vol. 2, pp. 360–362, 2011. View at Publisher · View at Google Scholar
  92. A. Boni, A. P. Cogdill, P. Dang et al., “Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function,” Cancer Research, vol. 70, no. 13, pp. 5213–5219, 2010. View at Publisher · View at Google Scholar · View at Scopus