Skip to main content
SpringerLink
Log in

Improving Outcomes in Advanced Malignant Melanoma

Update on Systemic Therapy

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Malignant melanoma continues to increase in incidence throughout the developed world. Surgery remains the cornerstone of curative treatment and the use of adjuvant systemic therapy has provoked much debate. Metastatic disease is incurable in most patients. While combination chemotherapy or biochemotherapy may be considered in certain circumstances, it is now clear that single-agent chemotherapy remains the mainstay of treatment for the majority of patients.

A number of new agents and novel approaches are under evaluation and show promise. The pro-apoptotic agent oblimersen has shown improved progressionfree survival and response rate, although not overall survival, when combined with dacarbazine compared with dacarbazine alone. The BRaf inhibitor sorafenib (BAY 43-9006) has produced encouraging results when administered with chemotherapy and is now being assessed in randomised studies. Thalidomide in combination with chemotherapy is well tolerated and shows a trend towards increased clinical efficacy compared with chemotherapy alone. Other anti-angiogenic drugs, such as bevacizumab, are being investigated in trials. Results with tumour vaccines have been mixed and several large trials are ongoing.

This paper discusses recent pivotal studies and promising new agents in systemic therapy for advanced malignant melanoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

References

  1. De Vries E, Bray FI, Coebergh JW, et al. Changing epidemiology of malignant cutaneous melanoma in Europe 1953–1997: rising trends in incidence and mortality but recent stabilisations in Western Europe and decreases in Scandanavia. Int J Cancer 2003; 107(1): 119–26

    Article  PubMed  Google Scholar 

  2. MacKie RM, Bray CA, Hole DJ, et al. Incidence of and survival from malignant melanoma in Scotland: an epidemiological study. Lancet 2002; 360: 587–91

    Article  PubMed  Google Scholar 

  3. Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin 2003; 53: 5–26

    Article  PubMed  Google Scholar 

  4. Giles D, Dwyer T, Coates M, et al. Trends in skin cancer in Australia: an overview of the available data. Trans Menzies Found 1989; 15: 143–7

    Google Scholar 

  5. Morton DL, Essner R, Calch C. Surgical excision of distant metastases. In: Balch C, Houghton A, Sober A, et al., editors. Cutaneous melanoma. 4th ed. St Louis (MO): Quality Medical Publishing, 2003: 547–72

    Google Scholar 

  6. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging for cutaneous melanoma. J Clin Oncol 2001; 19: 3635–48

    PubMed  CAS  Google Scholar 

  7. Middleton MR, Grob JJ, Aaronson N, et al. Randomised phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic melanoma. J Clin Oncol 2000; 18: 158–66

    PubMed  CAS  Google Scholar 

  8. Millward MJ, Bedikian AY, Conry RM, et al. Randomised multinational phase 3 trial of dacarbazine with or without bcl-2 antisense (oblimersan sodium) in patients with advanced malignant melanoma: analysis of long-term survival [abstract no. 7505]. Proc Am Soc Clin Oncol 2004; 22(145): 22

    Google Scholar 

  9. Lee SM, Betticher DC, Thatcher N. Melanoma: chemotherapy. Br Med Bull 1995; 51: 609–30

    PubMed  CAS  Google Scholar 

  10. Luikart SD, Kennealey GT, Kirkwood JM. Randomised phase III trial of vinblastine, bleomycin and cis-dichlorodiamineplatinum versus dacarbazine in malignant melanoma. J Clin Oncol 1984; 2: 164–8

    PubMed  CAS  Google Scholar 

  11. Chapman PB, Einhorn LH, Meyers ML, et al. Phase III multicentre randomised trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999; 17: 2745–51

    PubMed  CAS  Google Scholar 

  12. Middleton M, 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: 1158–62

    Article  PubMed  CAS  Google Scholar 

  13. Legha SS. The role of interferon alpha in the treatment of metastatic melanoma. Semin Oncol 1997; 24 (4 Suppl.): S24–31

    PubMed  CAS  Google Scholar 

  14. Agarwala SS, Glaspy J, O’Day SJ, et al. Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma. J Clin Oncol 2002; 20: 125–33

    Article  PubMed  CAS  Google Scholar 

  15. 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: 2105–16

    PubMed  CAS  Google Scholar 

  16. Margolin K, Atkins M, Sparano J, et al. Prospective randomised trial of lisofylline for the prevention of toxicities of high dose interleukin-2 therapy in advanced renal cancer and malignant melanoma. Clin Cancer Res 1997; 3: 365–72

    Google Scholar 

  17. Falkson C, Falkson G, Falkson H. Improved results with the addition of interferon alpha-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol 1991; 9: 1403–8

    PubMed  CAS  Google Scholar 

  18. Huncharek M, Caubet JF, McGarry R. Single-agent dacarbazine versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials. Melanoma Res 2001; 11: 75–81

    Article  PubMed  CAS  Google Scholar 

  19. Keilholz U, Conradt C, Legha SS, et al. Results of interleukin-2 based treatment in advanced melanoma: a case record-based analysis of 631 patients. J Clin Oncol 1998; 16(9): 2921–9

    PubMed  CAS  Google Scholar 

  20. Ernstoff MS. Update: medical therapy for cutaneous melanoma [oral presentation]. American Society of Clinical Oncology (ASCO) 39th Annual Meeting; 2003 May 31–Jun 3; Chicago

  21. Del Vecchio M, Bajetta E, Vitali M, et al. Multicentre phase III randomised trial of cisplatin, vindesine and dacarbazine (CVD) versus CVD plus subcutaneous (sc) interleukin-2 (IL-2) and interferon-alpha-2b (IFN) in metastatic melanoma patients (pts) [abstract no. 2849]. American Society of Clinical Oncology (ASCO) 39th Annual Meeting; 2003 May 31–Jun 3; Chicago

  22. Keilholz U, Punt CJ, Gore M, et al. Dacarbazine, cisplatin and IFN-alpha-2b with or without IL-2 in advanced melanoma: final analysis of EORTC randomised phase III trial 18951 [abstract no. 2848]. American Society of Clinical Oncology (ASCO) 39th Annual Meeting; 2003 May 31–Jun 3; Chicago

  23. Atkins MB, Lee S, Flaherty LE, et al. A prospective randomised 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 [abstract no. 2847]. Proc Am Soc Clin Oncol 2003; 22: 708

    Google Scholar 

  24. Newlands ES, Blackledge GR, Slack JA, et al. Phase I trial of temozolomide (CCRG 81045: Mß 39831: NSC 362856). Br J Cancer 1992; 65: 287–91

    Article  PubMed  CAS  Google Scholar 

  25. Bleehan NM, Newlands ES, Lee SM, et al. Cancer Research Campaign phase II trial of temozolomide in malignant melanoma. J Clin Oncol 1995; 13: 910–3

    Google Scholar 

  26. Lee SM, Thatcher N, Crowther D, et al. Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. Br J Cancer 1994; 69: 452–6

    Article  PubMed  CAS  Google Scholar 

  27. Su YB, Sohn S, Krown SE, et al. Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications. J Clin Oncol 2004; 22(3): 610–6

    Article  PubMed  CAS  Google Scholar 

  28. Yung WK, Levin VA, Albright J, et al. A phase II study of temozolomide vs procarbazine in glioblastoma multiforme at first relapse. Br J Cancer 2000; 83: 588–93

    Article  PubMed  CAS  Google Scholar 

  29. Villa S, Verger E, Gil M, et al. Concomitant and adjuvant temozolomide and whole brain irradiation on patients affected with brain metastases: a randomised multicentre phase II trial. Int J Radiat Oncol 2003; 57 (2 Suppl.): S132

    Article  Google Scholar 

  30. Stupp R, Mason WP, Van Den Bent MJ, et al. Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme: conclusive results of a randomised phase III trial by the EORTC brain and RT groups and NCIC clinical trials group [abstract no. 2]. Proc Am Soc Clin Oncol 2004; 22(145): 15

    Google Scholar 

  31. Paul MJ, Summers Y, Calvert H, et al. Effect of temozolomide on central nervous system relapse in patients with advanced melanoma. Melanoma Res 2002; 12(2): 175–8

    Article  PubMed  CAS  Google Scholar 

  32. Agarwala SS, Kirkwood JM, Gore M, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol 2004; 22: 2101–7

    Article  PubMed  CAS  Google Scholar 

  33. Kleeburg UR, Engel E, Israels P, et al. Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and effectiveness: a multi-centre phase II trial of the EORTC-melanoma cooperative group (MCG). Melanoma Res 1995; 5: 195–200

    Google Scholar 

  34. Avril MF, Aamdal S, Grob JJJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 2004; 22: 1118–25

    Article  PubMed  CAS  Google Scholar 

  35. Middleton MR, Lee SM, Arance A, et al. O6-methylguanine formation, repair protein depletion and clinical outcome with a 4 hr schedule of temozolomide in the treatment of advanced melanoma: results of a phase II study. Int J Cancer 2000; 88(3): 469–73

    Article  PubMed  CAS  Google Scholar 

  36. Dolan ME, Posner M, Karrison T, et al. Determination of the optimal modulatory dose of O6-benzylguanine in patients with surgically respectable tumours. Clin Cancer Res 2002; 8: 2519–23

    PubMed  CAS  Google Scholar 

  37. Tentori L, Leonetti C, Scarsella M, et al. Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumour activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 2003; 9: 5370–9

    PubMed  CAS  Google Scholar 

  38. Hu Y, Cherton-Horvat G, Dragowska V, et al. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res 2003; 9(7): 2826–36

    PubMed  CAS  Google Scholar 

  39. Amiri KI, Horton LW, LaFleur BJ, et al. Augmenting chemosensitivity of malignant melanoma tumours via proteasome inhibition: implication for bortezomib (VELCADE, PS-341) as a therapeutic agent for malignant melanoma. Cancer Res 2004; 64: 4912–8

    Article  PubMed  CAS  Google Scholar 

  40. Eisen T, Boshoff C, Mak I, et al. Continuous low dose thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 2000; 14 (13 Suppl.): 17–20

    CAS  Google Scholar 

  41. Danson S, Lorigan P, Arance A, et al. A randomised study of temozolomide (TMZ) alone, with interferon (TMZ-IFN) or with thalidomide (TMZ-THAL) in metastatic malignant melanoma (MMM). J Clin Oncol 2003; 21(13): 2551–7

    Article  PubMed  CAS  Google Scholar 

  42. Hwu WJ, Krown SE, Menell JH, et al. Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma. J Clin Oncol 2003; 21(17): 3351–6

    Article  PubMed  CAS  Google Scholar 

  43. Dredge K, Marriott JB, Macdonald CD, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 2002; 87(10): 1166–72

    Article  PubMed  CAS  Google Scholar 

  44. Bartlett JB, Michael A, Clarke IA, et al. Phase I study to determine the safety, tolerability and immunostimulatory activity of the thalidomide analogue CC-5013 in patients with metastatic melanoma and other advanced cancers. Br J Cancer 2004; 90(5): 955–61

    Article  PubMed  CAS  Google Scholar 

  45. Tucker GC. Alpha v integrin inhibitors and cancer therapy [erratum appears in Curr Opin Investig Drugs 2003; 4: 1140]. Curr Opin Investig Drugs. 2003 Jun; 4(6): 722–31

    PubMed  CAS  Google Scholar 

  46. Peterson AC, Swiger S, Stadler W, et al. Phase II study of the Flk-1 tyrosine kinase inhibitor SU5416 in patients with advanced melanoma [abstract no. 2863]. Proc Am Soc Clin Oncol 2003; 22: 712

    Google Scholar 

  47. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal carcinoma. N Engl J Med 2004; 350(23): 2335–42

    Article  PubMed  CAS  Google Scholar 

  48. Carsons WE, Biber J, Shah N, et al. A phase 2 trial of a recombinant humanised monoclonal anti-vascular endothelial growth factor (VEGF) antibody in patients with malignant melanoma [abstract no. 2873]. Proc Am Soc Clin Oncol 2003; 22: 715

    Google Scholar 

  49. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949–54

    Article  PubMed  CAS  Google Scholar 

  50. Casula M, Colombino M, Satta MP, et al. BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup Study. J Clin Oncol 2004; 22(2): 286–92

    Article  PubMed  CAS  Google Scholar 

  51. Rivers JK. Is there more than one road to melanoma? Lancet 2004; 363: 728–30

    Article  PubMed  Google Scholar 

  52. Hingorani SR, Jacobetz MA, Robertson GP, et al. Suppression of BRAFV599E in human melanoma abrogates transformation. Cancer Res 2003; 63: 5198–202

    PubMed  CAS  Google Scholar 

  53. Collisson EA, De A, Suzuki H, et al. Treatment of metastatic melanoma with an orally available inhibitor of the ras-raf-MAPK cascade. Cancer Res 2003; 63: 5669–73

    PubMed  CAS  Google Scholar 

  54. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumour activity and targets the RAF/ MEK/ERK pathway and receptor tyrosine kinases involved in tumour progression and angiogenesis. Cancer Res 2004; 64: 7099–109

    Article  PubMed  CAS  Google Scholar 

  55. Ahmad T, Marais R, Pyle L, et al. BAY 43-9006 in patients with advanced melanoma: the Royal Marsden experience [abstract no. 7506]. Proc Am Soc Clin Oncol 2004; 22(145): 7115

    Google Scholar 

  56. Flaherty KT, Brose M, Schuchter L, et al. Phase I/II trial of BAY 43-9006, carboplatin and paclitaxel demonstrates preliminary antitumour activity in the expansion cohort patients with metastatic melanoma [abstract no. 7507]. Proc Am Soc Clin Oncol 2004; 22(145): 7115

    Google Scholar 

  57. Sparrow LE, Heenan PJ. Differential expression of epidermal growth factor receptor melanocytic tumours demonstrated by immunohistochemistry and mRNA in situ hybridization. Australas J Dermatol 1999; 40(1): 19–24

    Article  PubMed  CAS  Google Scholar 

  58. Inman JL, Kute T, White W. Absence of HER2 overexpression in metastatic malignant melanoma. J Surg Oncol 2003; 84(2): 82–8

    Article  PubMed  Google Scholar 

  59. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukaemia. N Engl J Med 2001; 344: 1031–7

    Article  PubMed  CAS  Google Scholar 

  60. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumours. N Engl J Med 2002; 347: 472–80

    Article  PubMed  CAS  Google Scholar 

  61. Janku F, Tomancova V, Novotny J, et al. Expression of c-kit was found in more than 50% of early stages melanoma: a retrospective study of 261 patients [abstract no. 2864]. Proc Am Soc Clin Oncol 2003; 22: 712

    Google Scholar 

  62. Wyman K, Atkins MB, Hubbard F, et al. A phase II trial of imatinib mesylate at 800mg daily in metastatic melanoma: lack of clinical efficacy with significant toxicity [abstract no. 2865]. Proc Am Soc Clin Oncol 2003; 22: 713

    Google Scholar 

  63. National Cancer Institute (NCI). Clinical trials [online]. Available from URL: http://www.cancer.gov/search/clinicaltrials [Accessed 2005 Feb 2]

  64. Hansson M, Hermodsson S, Brune M, et al. Histamine protects T cells and natural killer cells against oxidative stress. J Interferon Cytokine Res 1999; 19: 1135–44

    Article  PubMed  CAS  Google Scholar 

  65. Asea A, Hermodsson S, Hellstrand K. Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice. Scand J Immunol 1996; 43: 9–15

    Article  PubMed  CAS  Google Scholar 

  66. Hellstrand K, Naredi P, Lindner P, et al. Histamine in immunotherapy of advanced melanoma: a pilot study. Cancer Immunol Immunother 1994; 39: 416–9

    Article  PubMed  CAS  Google Scholar 

  67. Maxim Pharmaceuticals Press Conference. Maxim Pharmaceutical phase 3 trial for advanced melanoma fails to meet primary endpoint [media release]. 2004 Sep 20

  68. Hauschild A. First analysis of international M-02 trial: histamine, interferon alpha-2b (IFN), interleukin (IL)-2 vs dacarbazine (DTIC) [oral presentation]. European conference: Perspectives in Melanoma Management; 2003 Oct 10–11; Amsterdam

  69. Sosman JA, Weeraranta AT, Sondak VK. When will melanoma vaccines be proven effective? J Clin Oncol 2004; 22(3): 387–9

    Article  PubMed  CAS  Google Scholar 

  70. Livingstone PO, Wong GY, Adluri S, et al. Improved survival in stage III melanoma patients with GM2 antibodies, a randomised trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 1994; 5: 1036–44

    Google Scholar 

  71. Kirkwood JM, Ibrahim JG, Sosman JA, et al. High dose interferon alpha 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(9): 2370–80

    PubMed  CAS  Google Scholar 

  72. Marchard M, von Baren N, Weynants P, et al. Tumour regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al. Int J Cancer 1999; 80: 219–30

    Article  Google Scholar 

  73. Cebon J, Jager E, Shackleton MJ, et al. Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenze peptides in subjects with advanced malignant melanoma. Cancer Immun 2003; 16: 3–7

    Google Scholar 

  74. Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 1998; 4: 321–7

    Article  PubMed  CAS  Google Scholar 

  75. Kirkwood J, Lee S, Land S, et al. E1696: final analysis of the clinical and immunological results of a multi-centre ECOG phase II trial of multi-epitope peptide vaccination for stage IV disease with MART-1, gp1000 and tyrosinase [abstract no. 7502]. Proc Am Soc Clin Oncol 2004; 22(145): 7105

    Google Scholar 

  76. David I, Chen W, Jackson H, et al. Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans. Proc Natl Acad Sci U S A 2004; 101: 10697–702

    Article  Google Scholar 

  77. Sosman JA, Unger JM, Liu PY, et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumour vaccine: impact of HLA class I antigen expression on outcome. Southwest Oncology Group. J Clin Oncol 2002; 20(8): 2067–75

    CAS  Google Scholar 

  78. Morton DL, Eilber FR, Holmes EC, et al. Preliminary results of a randomised trial of adjuvant immunotherapy in patients treated with malignant melanoma who have lymph node metastases. Aust N Z J Surg 1978; 48: 49–52

    Article  PubMed  CAS  Google Scholar 

  79. Chan AD, Morton DL. Active immunotherapy with allogeneic tumour cell vaccines: present status. Semin Oncol 1998; 25: 611–22

    PubMed  CAS  Google Scholar 

  80. Belli F, Testori A, Rivoltini L, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol 2002; 20(20): 4169–80

    Article  PubMed  CAS  Google Scholar 

  81. Soiffer R, Hodi FS, Haluska F, et al. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J Clin Oncol 2003; 21(17): 3343–50

    Article  PubMed  CAS  Google Scholar 

  82. Smith CL, Dunbar PR, Palmowski MJ, et al. Results of a phase I study evaluating ‘prime-boost’ therapeutic vaccination strategies using a string of melanoma-derived CD8+ T cell epitopes in stage II/III/IV melanoma patients [abstract no. 702]. Proc Am Soc Clin Oncol 2003; 22: 175

    Article  Google Scholar 

  83. Smith C, Dunbar P, Mirza F, et al. Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. Int J Cancer 2005; 113(2): 259–66

    Article  PubMed  CAS  Google Scholar 

  84. Kugler A, Stuhler G, Waiden P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumour cell-dendritic cell hybrids. Nat Med 2000; 6: 332–6

    Article  PubMed  CAS  Google Scholar 

  85. Bedrosian I, Mick R, Xu S, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 2003; 21(20): 3826–35

    Article  PubMed  CAS  Google Scholar 

  86. Schadendorf D, Nestle FO, Broecker E-B, et al. Dacarbazine versus vaccination with autologous peptide-pulsed dendritic cells as first-line treatment of patients with metastatic melanoma: results of a prospective-randomised phase III study [abstract no. 7508]. Proc Am Soc Oncol 2004; 22(145): 7125

    Google Scholar 

  87. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumour lymphocytes. Science 2002; 298: 850–4

    Article  PubMed  CAS  Google Scholar 

  88. Phan GQ, Yang J, Sherry RM, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen4 blockade in patients with metastatic melanoma. Proc Nat Acad Sci U S A 2003; 100: 8372–7

    Article  CAS  Google Scholar 

  89. Hersh E, Weber J, Powderly J, et al. A phase II randomised multi-centre study of MDX-010 alone or in combination with DTIC in stage IV malignant melanoma [abstract no. 7511]. Proc Am Soc Clin Oncol 2004; 22(145): 7125

    Google Scholar 

  90. Schneeder A, Wagner C, Zemann A, et al. CpG motifs are efficient adjuvants for DNA vaccines. J Invest Dermatol 2004; 123: 371–9

    Article  Google Scholar 

Download references

Acknowledgements

Dr Lorigan has received honoraria from Aventis and from Schering Plough for advisory board work, research support from Genta, and educational grants from Aventis and Schering Plough. Dr Danson has received educational support from Schering Plough. No sources of funding were used to assist in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Christie Hospital NHS Trust, Withington, Wilmslow Road, Manchester, M20 4BX, UK

    Sarah Danson & Paul Lorigan

Authors
  1. Sarah Danson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Lorigan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah Danson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Danson, S., Lorigan, P. Improving Outcomes in Advanced Malignant Melanoma. Drugs 65, 733–743 (2005). https://doi.org/10.2165/00003495-200565060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200565060-00002

Keywords

Search

Navigation