Skip to main content

Melanoma

  • Chapter
  • First Online:
Skin Cancer - A World-Wide Perspective

Abstract

Historically, melanoma patients were subject to wide local excisions and elective lymph node dissections (ELND). Both approaches have been the focus of intense scrutiny over the past three decades, and many surgical dogmas were abolished. The role of surgery in providing local control over the primary tumor is largely undisputed. However, surgical management strategies of the regional lymph nodes (RLN) have undergone considerable change in the past, with lymphatic mapping and sentinel lymph node (SLN) identification being the most relevant contribution, allowing for selection of patients for adjuvant treatment (completion lymph node dissection, Interferon therapy). Surgery has also a place in palliative treatment of isolated systemic metastases for select cases of stage IV melanoma in which the patient displays a good performance status.

In the past decades, the incidence of cutaneous malignant melanoma has risen steadily, faster than all cancers except lung cancer, accompanied by an increase in mortality in male patients [1]. It accounts for the sixth highest number of newly diagnosed cancer cases and is the sixth most common cancer among men and seventh most common among women [2]. Due to major prevention efforts, the numbers seem to have stabilized in younger age groups [1]. Early diagnosis has increased the proportion of thin melanomas with a higher cure rate [3]. However, overall melanoma-specific survival remains unaffected, despite all efforts towards improving medical care. Historically, melanoma patients were subject to wide local excisions and ELND. Both approaches have been the focus of intense scrutiny over the past three decades, and many surgical dogmas were abolished. The role of surgery in providing local control over the primary tumor is largely undisputed. However, the surgical management strategies of the regional lymph nodes (RLN) have undergone considerable change in the past, with lymphatic mapping and SLN identification being the most relevant contribution [4]. Today, SNB is the most important staging tool, because the status of the SLN represents the most important prognostic factor for recurrence and survival in melanoma patients and identifies patients who might benefit from further therapy, such as completion lymph node dissection (CLND) and adjuvant interferon therapy [5, 6]. Nevertheless, the impact of sentinel lymph node biopsy (SLNB) and CLND on survival remains unclear. Surgery also has a place in palliative treatment of systemic metastases in stage IV melanoma. Surgery of visceral metastases may be appropriate for select cases of good patient performance status and isolated tumor manifestation.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

Surgery

  1. Mackie, R.M., Bray, C., Vestey, J., et al.: Melanoma incidence and mortality in Scotland 1979–2003. Br J Cancer 96, 1772 (2007)

    Article  CAS  PubMed  Google Scholar 

  2. Cancer Facts and Figures. Available at: http://www.cancer.org (2007)

  3. McMasters, K.M., Swetter, S.M.: Current management of melanoma: benefits of surgical staging and adjuvant therapy. J Surg Oncol 82, 209 (2003)

    Article  PubMed  Google Scholar 

  4. Morton, D.L., Wen, D.R., Wong, J.H., et al.: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127, 392 (1992)

    Article  CAS  PubMed  Google Scholar 

  5. Balch, C.M., Soong, S.J., Gershenwald, J.E., et al.: Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19, 3622 (2001)

    CAS  PubMed  Google Scholar 

  6. Eggermont, A.M., Santinami, M., Kruit, W., et al.: Therapy with pegylated interferon α-2b versus observation in resected stage III melanoma: final results of EORTC 18991, a randomised phase 3 trial. Lancet (2008)

    Google Scholar 

  7. Dummer, R., Panizzon, R., Bloch, P.H., Burg, G.: Updated Swiss guidelines or the treatment and follow-up of cutaneous melanoma. Dermatology 210, 39 (2005)

    Article  CAS  PubMed  Google Scholar 

  8. Handley, W.: The pathology of melanotic growths in relation to their operative treatment. Lancet 1, 927–933 (1907)

    Google Scholar 

  9. Veronesi, U., Cascinelli, N., Adamus, J., et al.: Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm. N Engl J Med 318, 1159–1162 (1988)

    Article  CAS  PubMed  Google Scholar 

  10. Cohn-Cedermark, G., Lars, E.R., Andersson, R., et al.: Long term results of a randomized study by the Swedish melanoma study group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8–2.0mm. Cancer 89(7), 1495–1501 (2000)

    Article  CAS  PubMed  Google Scholar 

  11. Khayat, D., Rixe, O., Martin, G.: Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring less then 2.1-mm thick). Long-term results of a large European multicentric phase III study. Cancer 97, 941–1946 (2003)

    Article  Google Scholar 

  12. Balch, C.M., Urist, M.M., Karakousis, C.P., et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 MM). Results of a multi-institutional randomized surgical trial. Ann Surg 218, 262–269 (1993)

    Article  CAS  PubMed  Google Scholar 

  13. Thomas, J.M., Newton-Bishop, J., A’Hern, R., et al.: Excision margins in high-risk malignant melanoma. N Engl J Med 350, 757–766 (2004)

    Article  CAS  PubMed  Google Scholar 

  14. Morton, D.L., Thompson, J.F., Essner, R., et al.: Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg 230, 453–463 (1999)

    Article  CAS  PubMed  Google Scholar 

  15. Morton, D.L., Thompson, J.F., Cochran, A.J., Mozzillo, N., Elashoff, R., Essner, R., Nieweg, O.E., Roses, D.F., Hoekstra, H.J., Karakousis, C.P., Reintgen, D.S., Coventry, B.J., Glass, E.C., Wang, H.J.: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355, 1307 (2006)

    Article  CAS  PubMed  Google Scholar 

  16. Balch, C.M., Morton, D.L., Gershenwald, J.E., et al.: Sentinel node biopsy and standard of care for melanoma. J Am Acad Dermatol 60, 872–875 (2009)

    Article  PubMed  Google Scholar 

  17. McMasters, K.M.: What good is sentinel lymph node biopsy for melanoma if it does not improve survival? Ann Surg Oncol 11, 810–812 (2004)

    Article  PubMed  Google Scholar 

  18. Bleicher, R.J., Essner, R., Foshag, L.J., et al.: Role of sentinel lymphadenectomy in thin invasive cutaneous melanomas. J Clin Oncol 21, 1326–1331 (2003)

    Article  PubMed  Google Scholar 

  19. Cochran, A.J., Balda, B.R., Starz, H., et al.: The Augsburg Consensus. Techniques of lymphatic mapping, sentinel lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies. Cancer 89, 236–241 (2000)

    Article  CAS  PubMed  Google Scholar 

  20. Yao, K., Balch, G., Winchester, D.J.: Multidisciplinary treatment of primary melanoma. Surg Clin North Am 89, 267–281 (2009)

    Article  PubMed  Google Scholar 

  21. Pharis, D.B.: Cutaneous melanoma: therapeutic lymph node and elective lymph node dissections, lymphatic mapping and sentinel lymph node biopsy. Dermatol Ther 18, 397–406 (2005)

    Article  PubMed  Google Scholar 

  22. Wrightson, W.R., Wong, S.L., Edwards, M.J., et al.: Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol 10, 676–680 (2003)

    Article  PubMed  Google Scholar 

  23. Gutzmer, R., Al Ghazal, M., Geerlings, H., et al.: Sentinel node biopsy in melanoma delays recurrence but does not change melanoma-related survival: a retrospective analysis of 673 patients. Br J Dermatol 153, 1137–1141 (2005)

    Article  CAS  PubMed  Google Scholar 

  24. Van Akkooi, A.C., De Wilt, J.H., Verhoef, C., et al.: Clinical relevance of melanoma micrometastases (<0.1mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol 17, 1578 (2006)

    Article  PubMed  Google Scholar 

  25. Guggenheim, M., Dummer, R., Jung, F.J., et al.: The influence of sentinel lymph node tumor burden on additional lymph node involvement and disease-free survival in cutaneous melanoma–a retrospective analysis of 392 cases. Br J Cancer 98, 1922–1928 (2009)

    Article  Google Scholar 

  26. Cascinelli, N., Bombardieri, E., Bufalino, R., Camerini, T., Carbone, A., Clemente, C., Lenisa, L., Mascheroni, L., Maurichi, A., Pennacchioli, E., Patuzzo, R., Santinami, M., Tragni, G.: Sentinel and nonsentinel node status in stage IB and II melanoma patients: two-step prognostic indicators of survival. J Clin Oncol 24, 4464 (2006)

    Article  PubMed  Google Scholar 

  27. Scolyer, R.A., Murali, R., Gershenwald, J.E., et al.: Clinical relevance of melanoma micrometastases in sentinel nodes: too early to tell. Ann Oncol 18, 806 (2007)

    Article  CAS  PubMed  Google Scholar 

  28. Satzger, I., Volker, B., Meier, A., et al.: Prognostic significance of isolated HMB45 or Melan A positive cells in Melanoma sentinel lymph nodes. Am J Surg Pathol 31, 1175 (2007)

    Article  PubMed  Google Scholar 

  29. Meyer, T., Merkel, S., Goehl, J., Hohenberger, W.: Surgical therapy for distant metastases of malignant melanoma. Cancer 89, 1983–1991 (2000)

    Article  CAS  PubMed  Google Scholar 

  30. Dummer, R., Hauschild, A., Jost, L.: ESMO Guidelines Working Group. Cutaneous malignant melanoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 19(suppl 2), ii86–ii88 (2008)

    Article  PubMed  Google Scholar 

  31. Kroon, H.M., Thompson, J.F.: Isolated limb infusion: a review. J Surg Oncol 100, 169–177 (2009)

    Article  PubMed  Google Scholar 

  32. Zacest, A.C., Besser, M., Stevens, G., et al.: Surgical management of cerebral metastases from melanoma: outcome in 147 patients treated at a single institution over two decades. J Neurosurg 96, 552–558 (2002)

    Article  PubMed  Google Scholar 

  33. Selek, U., Chang, E.L., Hassenbusch III, S.J., et al.: Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys 59, 1097–1106 (2004)

    Article  PubMed  Google Scholar 

  34. Uren, R.F.: SPECT/CT lymphoscintigraphy to locate the sentinel lymph node in patients with melanoma. Ann Surg Oncol 16, 1459–1460 (2009)

    Article  PubMed  Google Scholar 

  35. Morton, D.L., Thompson, J.F., Essner, R., et al.: Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma. A multicenter trial. Ann Surg 230, 453 (1999)

    Article  CAS  PubMed  Google Scholar 

  36. Cook, M.G., Green, M.A., Anderson, B., et al.: The development of optimal pathological assessment of sentinel lymph nodes for melanoma. J Pathol 200, 314 (2003)

    Article  PubMed  Google Scholar 

  37. Mack, L.A., McKinnon, J.G.: Controversies in the management of metastatic melanoma to regional lymphatic basins. J Surg Oncol 86, 189–199 (2004)

    Article  PubMed  Google Scholar 

  38. Guggenheim, M.M., Hug, U., Jung, F.J., et al.: Morbidity and recurrence after completion lymph node dissection following sentinel lymph node biopsy in cutaneous malignant melanoma. Ann Surg 247, 687 (2008)

    Article  PubMed  Google Scholar 

  39. Karakousis, C.P., Hena, M.A., Emrich, L.J., et al.: Axillary node dissection in malignant melanoma: results and complications. Surgery 108, 10–17 (1990)

    CAS  PubMed  Google Scholar 

  40. Chan, A.R., Essner, R., Wanek, L.A., et al.: Judging the therapeutic value of lymph node dissections in melanoma. J Am Coll Surg 191, 16–23 (2000)

    Article  CAS  PubMed  Google Scholar 

Radiation

  1. Andrews, D.W., Scott, C.W., Sperduto, P.W., et al.: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363, 1665–1672 (2004)

    Article  PubMed  Google Scholar 

  2. Ang, K.K., Byers, R.M., Peters, L.J., Maor, M.H., Wendt, C.D., Morrison, W.H., Hussey, D.H., Goepfert, H.: Regional radiotherapy as adjuvant treatment for head and neck malignant melanoma. Preliminary results. Arch Otolaryngol Head Neck Surg 116, 169–172 (1990)

    Article  CAS  PubMed  Google Scholar 

  3. Ang, K.K., Peters, L.J., Weber, R.S., Morrison, W.H., Frankenthaler, R.A., Garden, A.S., Goepfert, H., Ha, C.S., Byers, R.M.: Postoperative radiotherapy for cutaneous melanoma of the head and neck region. Int J Radiat Oncol Biol Phys 30, 795–798 (1994)

    Article  CAS  PubMed  Google Scholar 

  4. Ballo, M.T., Strom, E.A., Zagars, G.K., Bedikian, A.Y., Prieto, V.G., Mansfield, P.F., Lee, J.E., Gershenwald, J.E., Ross, M.I.: Adjuvant irradiation for axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys 52, 964–972 (2002)

    Article  PubMed  Google Scholar 

  5. Ballo, M.T., Bonnen, M.D., Garden, A.S., Myers, J.N., Gershenwald, J.E., Zagars, G.K., Schechter, N.R., Morrison, W.H., Ross, M.I., Kian Ang, K.: Adjuvant irradiation for cervical lymph node metastases from melanoma. Cancer 97, 1789–1796 (2003)

    Article  PubMed  Google Scholar 

  6. Ballo, M.T., Zagars, G.K., Gershenwald, J.E., Lee, J.E., Mansfield, P.F., Kim, K.B., Camacho, L.H., Hwu, P., Ross, M.I.: A critical assessment of adjuvant radiotherapy for inguinal lymph node metastases from melanoma. Ann Surg Oncol 11, 1079–1084 (2004)

    Article  PubMed  Google Scholar 

  7. Ballo, M.T., Garden, A.S., Myers, J.N., Lee, J.E., Diaz Jr., E.M., Sturgis, E.M., Morrison, W.H., Gershenwald, J.E., Ross, M.I., Weber, R.S., Ang, K.K.: Melanoma metastatic to cervical lymph nodes: can radiotherapy replace formal dissection after local excision of nodal disease? Head Neck 27, 718–721 (2005)

    Article  PubMed  Google Scholar 

  8. Ballo, M.T., Ross, M.I., Cormier, J.N., Myers, J.N., Lee, J.E., Gershenwald, J.E., Hwu, P., Zagars, G.K.: Combined-modality therapy for patients with regional nodal metastases from melanoma. Int J Radiat Oncol Biol Phys 64, 106–113 (2006)

    Article  PubMed  Google Scholar 

  9. Beadle, B.M., Guadagnolo, B.A., Ballo, M.T., Lee, J.E., Gershenwald, J.E., Cormier, J.N., Mansfield, P.F., Ross, M.I., Zagars, G.K.: Radiation therapy field extent for adjuvant treatment of axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys 73, 1376–1382 (2009)

    Article  PubMed  Google Scholar 

  10. Bonnen, M.D., Ballo, M.T., Myers, J.N., Garden, A.S., Diaz Jr., E.M., Gershenwald, J.E., Morrison, W.H., Lee, J.E., Oswald, M.J., Ross, M.I., Ang, K.K.: Elective radiotherapy provides regional control for patients with cutaneous melanoma of the head and neck. Cancer 100, 383–389 (2004)

    Article  PubMed  Google Scholar 

  11. Burmeister, B.H., Smithers, B.M., Poulsen, M., McLeod, G.R., Bryant, G., Tripcony, L., Thorpe, C.: Radiation therapy for nodal disease in malignant melanoma. World J Surg 19, 369–371 (1995)

    Article  CAS  PubMed  Google Scholar 

  12. Burmeister, B.H., Smithers, B.M., Davis, S., Spry, N., Johnson, C., Krawitz, H., Baumann, K.C.: Radiation therapy following nodal surgery for melanoma: an analysis of late toxicity. ANZ J Surg 72, 344–348 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. Burmeister, B.H., Mark Smithers, B., Burmeister, E., Baumann, K., Davis, S., Krawitz, H., Johnson, C., Spry, N., Trans Tasman Radiation Oncology Group: A prospective phase II study of adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma-Trans Tasman Radiation Oncology Group (TROG) Study 96.06. Radiother Oncol 81, 136–142 (2006)

    Article  PubMed  Google Scholar 

  14. Chang, D.T., Amdur, R.J., Morris, C.G., Mendenhall, W.M.: Adjuvant radiotherapy for cutaneous melanoma: comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys 66, 1051–1055 (2006)

    Article  PubMed  Google Scholar 

  15. Christie, D.R., Tiver, K.W.: Radiotherapy for melanotic freckles. Australas Radiol 40, 331–333 (1996)

    Article  CAS  PubMed  Google Scholar 

  16. Cooper, J.S., Chang, W.S., Oratz, R., Shapiro, R.L., Roses, D.F.: Elective radiation therapy for high-risk malignant melanomas. Cancer J 7, 498–502 (2001)

    CAS  PubMed  Google Scholar 

  17. Corry, J., Smith, J.G., Bishop, M., Ainslie, J.: Nodal radiation therapy for metastatic melanoma. Int J Radiat Oncol Biol Phys 44, 1065–1069 (1999)

    Article  CAS  PubMed  Google Scholar 

  18. Creagan, E.T., Cupps, R.E., Ivins, J.C., Pritchard, D.J., Sim, F.H., Soule, E.H., O’Fallon, J.R.: Adjuvant radiation therapy for regional nodal metastases from malignant melanoma: a randomized, prospective study. Cancer 42, 2206–2210 (1978)

    Article  CAS  PubMed  Google Scholar 

  19. Dancuart, F., Harwood, A.R., Fitzpatrick, P.J.: Radiotherapy of lentigo maligna and lentigo maligna melanoma of the head and neck. Cancer 45, 2279–2283 (1980)

    Article  CAS  PubMed  Google Scholar 

  20. Engin, K., Tupchong, L., Waterman, F.M., Moylan, D.J., Nerlinger, R.E., Leeper, D.B.: Hyperthermia and radiation in advanced malignant melanoma. Int J Radiat Oncol Biol Phys 25, 87–94 (1993)

    Article  CAS  PubMed  Google Scholar 

  21. Farshad, A., Burg, G., Panizzon, R., Dummer, R.: A retrospective study of 150 patients with lentigo maligna and lentigo maligna melanoma and the efficacy of radiotherapy using Grenz or soft X-rays. Br J Dermatol 146, 1042–1046 (2002)

    Article  CAS  PubMed  Google Scholar 

  22. Fenig, E., Eidelevich, E., Njuguna, E., Katz, A., Gutman, H., Sulkes, A., Schechter, J.: Role of radiation therapy in the management of cutaneous malignant melanoma. Am J Clin Oncol 22, 184–186 (1999)

    Article  CAS  PubMed  Google Scholar 

  23. Fife, K.M., Colman, M.H., Stevens, G.N., Firth, I.C., Moon, D., Shannon, K.F., Harman, R., Petersen-Schaefer, K., Zacest, A.C., Besser, M., Milton, G.W., McCarthy, W.H., Thompson, J.F.: Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol 22, 1293–1300 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. Foote, M.C., Burmeister, B., Burmeister, E., Bayley, G., Smithers, B.M.: Desmoplastic melanoma: the role of radiotherapy in improving local control. ANZ J Surg 78, 273–276 (2008)

    Article  PubMed  Google Scholar 

  25. Fuhrmann, D., Lippold, A., Borrosch, F., Ellwanger, U., Garbe, C., Suter, L.: Should adjuvant radiotherapy be recommended following resection of regional lymph node metastases of malignant melanomas? Br J Dermatol 144, 66–70 (2001)

    Article  CAS  PubMed  Google Scholar 

  26. Geara, F.B., Ang, K.K.: Radiation therapy for malignant melanoma. Surg Clin North Am 76, 1383–1398 (1996)

    Article  CAS  PubMed  Google Scholar 

  27. Golden, D.W., Lamborn, K.R., McDermott, M.W., Kunwar, S., Wara, W.M., Nakamura, J.L., Sneed, P.K.: Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. J Neurosurg 109(suppl), 77–86 (2008)

    PubMed  Google Scholar 

  28. Harwood, A.R.: Conventional fractionated radiotherapy for 51 patients with lentigo maligna and lentigo maligna melanoma. Int J Radiat Oncol Biol Phys 9, 1019–1021 (1983)

    Article  CAS  PubMed  Google Scholar 

  29. Harwood, A.R.: Radiotherapy of acral lentiginous melanoma of the foot. J La State Med Soc 151(7), 373–376 (1999)

    CAS  PubMed  Google Scholar 

  30. Harwood, A.R., Lawson, V.G.: Radiation therapy for melanomas of the head and neck. Head Neck Surg 4(6), 468–474 (1982)

    Article  CAS  PubMed  Google Scholar 

  31. Harwood, A.R., Dancuart, F., Fitzpatrick, P.J., Brown, T.: Radiotherapy in nonlentiginous melanoma of the head and neck. Cancer 48, 2599–2605 (1981)

    Article  CAS  PubMed  Google Scholar 

  32. Herbert, S.H., Solin, L.J., Rate, W.R., Schultz, D.J., Hanks, G.E.: The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. Cancer 67, 2472–2476 (1991)

    Article  CAS  PubMed  Google Scholar 

  33. Lagerwaard, F.J., Levendag, P.C., Nowak, P.J., Eijkenboom, W.M., Hanssens, P.E., Schmitz, P.I.: Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43, 795–803 (1999)

    Article  CAS  PubMed  Google Scholar 

  34. Lee, R.J., Gibbs, J.F., Proulx, G.M., Kollmorgen, D.R., Jia, C., Kraybill, W.G.: Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 46, 467–474 (2000)

    Article  CAS  PubMed  Google Scholar 

  35. Miescher, G.: Erfolge der Karzinombehandlung an der dermatologischen Klinik Zürich. Einzeitige Höchstdosis und fraktionierte Behandlung. Strahlentherapie 49, 65–81 (1934)

    Google Scholar 

  36. Moncrieff, M.D., Martin, R., O’Brien, C.J., Shannon, K.F., Clark, J.R., Gao, K., McCarthy, W.M., Thompson, J.F.: Adjuvant postoperative radiotherapy to the cervical lymph nodes in cutaneous melanoma: is there any benefit for high-risk patients? Ann Surg Oncol 15, 3022–3027 (2008)

    Article  PubMed  Google Scholar 

  37. Morris, K.T., Marquez, C.M., Holland, J.M., Vetto, J.T.: Prevention of local recurrence after surgical debulking of nodal and subcutaneous melanoma deposits by hypofractionated radiation. Ann Surg Oncol 7, 680–684 (2000)

    Article  CAS  PubMed  Google Scholar 

  38. Newlin, H.E., Morris, C.G., Amdur, R.J., Mendenhall, W.M.: Neurotropic melanoma of the head and neck with clinical perineural invasion. Am J Clin Oncol 28, 399–402 (2005)

    Article  PubMed  Google Scholar 

  39. O’Brien, C.J., Petersen-Schaefer, K., Stevens, G.N., Bass, P.C., Tew, P., Gebski, V.J., Thompson, J.F., McCarthy, W.H.: Adjuvant radiotherapy following neck dissection and parotidectomy for metastatic malignant melanoma. Head Neck 19, 589–594 (1997)

    Article  PubMed  Google Scholar 

  40. Overgaard, J., Overgaard, M.: Hyperthermia as an adjuvant to radiotherapy in the treatment of malignant melanoma. Int J Hyperthermia 3, 483–501 (1987)

    Article  CAS  PubMed  Google Scholar 

  41. Overgaard, J., von der Maase, H., Overgaard, M.: A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma. Int J Radiat Oncol Biol Phys 11, 1837–1839 (1985)

    Article  CAS  PubMed  Google Scholar 

  42. Overgaard, J., Gonzalez Gonzalez, D., Hulshof, M.C., Arcangeli, G., Dahl, O., Mella, O., Bentzen, S.M.: Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology. Int J Hyperthermia 12, 3–20 (1996)

    Article  CAS  PubMed  Google Scholar 

  43. Rate, W.R., Solin, L.J., Turrisi, A.T.: Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression. Int J Radiat Oncol Biol Phys 15, 859–864 (1988)

    Article  CAS  PubMed  Google Scholar 

  44. Richtig, E., Hoff, M., Rehak, P., Kapp, K., Hofmann-Wellenhof, R., Zalaudek, I., Poschauko, J., Uggowitzer, M., Kohek, P., Smolle, J.: Efficacy of superficial and deep regional hyperthermia combined with systemic chemotherapy and radiotherapy in metastatic melanoma. Dtsch Dermatol Ges 1, 635–642 (2003)

    Article  CAS  Google Scholar 

  45. Sampson, J.H., Carter Jr., J.H., Friedman, A.H., Seigler, H.F.: Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88, 11–20 (1998)

    Article  CAS  PubMed  Google Scholar 

  46. Sause, W.T., Cooper, J.S., Rush, S., Ago, C.T., Cosmatos, D., Coughlin, C.T., JanJan, N., Lipsett, J.: Fraction size in external beam radiation therapy in the treatment of melanoma. Int J Radiat Oncol Biol Phys 20, 429–432 (1991)

    Article  CAS  PubMed  Google Scholar 

  47. Schmid-Wendtner, M.H., Brunner, B., Konz, B., Kaudewitz, P., Wendtner, C.M., Peter, R.U., Plewig, G., Volkenandt, M.: Fractionated radiotherapy of lentigo maligna and lentigo maligna melanoma in 64 patients. J Am Acad Dermatol 43, 477–482 (2000)

    Article  CAS  PubMed  Google Scholar 

  48. Seegenschmiedt, M.H., Keilholz, L., Altendorf-Hofmann, A., Urban, A., Schell, H., Hohenberger, W., Sauer, R.: Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience. Int J Radiat Oncol Biol Phys 44(3), 607–618 (1999)

    Article  CAS  PubMed  Google Scholar 

  49. Shidnia, H., Hornback, N.B., Shen, R.N., Shupe, R.E., Yune, M.: An overview of the role of radiation therapy and hyperthermia in treatment of malignant melanoma. Adv Exp Med Biol 267, 531–545 (1990)

    Article  CAS  PubMed  Google Scholar 

  50. Stevens, G., Thompson, J.F., Firth, I., O’Brien, C.J., McCarthy, W.H., Quinn, M.J.: Locally advanced melanoma: results of postoperative hypofractionated radiation therapy. Cancer 88, 88–94 (2000)

    Article  CAS  PubMed  Google Scholar 

  51. Stevens, G., McKay, M.J.: Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma. Lancet Oncol 7(7), 575–583 (2006)

    Article  PubMed  Google Scholar 

  52. Tsang, R.W., Liu, F.F., Wells, W., Payne DG, L.: Lentigo maligna of the head and neck. Results of treatment by radiotherapy. Arch Dermatol 130, 1008–1012 (1994)

    Article  CAS  PubMed  Google Scholar 

  53. Tsao, M.N., Lloyd, N.S., Wong, R.K., Rakovitch, E., Chow, E., Laperriere, N., Supportive Care Guidelines Group of Cancer Care Ontario’s Program in Evidence-based Care: Radiotherapeutic management of brain metastases: a systematic review and meta-analysis. Cancer Treat Rev 31, 256–273 (2005)

    Article  PubMed  Google Scholar 

  54. von Essen, C.: Skin and lip. In: Fletcher, G.H. (ed.) Textbook of Radiotherapy, 3rd edn, pp. 271–285. Lea and Feibiger, Philadelphia (1980)

    Google Scholar 

  55. Vongtama, R., Safa, A., Gallardo, D., Calcaterra, T., Juillard, G.: Efficacy of radiation therapy in the local control of desmoplastic malignant melanoma. Head Neck 25, 423–428 (2003)

    Article  PubMed  Google Scholar 

Drug Therapy

  1. Oblimersen: Augmerosen, BCL-2 antisense oligonucleotide – Genta, G 3139, GC 3139, oblimersen sodium. Drugs R. D. 8, 321–334 (2007)

    Google Scholar 

  2. Amaravadi, R., Schuchter, L., McDermott, E.M.W., Kramer, A., Giles, L., Troxel, A.B., Medina, C.A., Nathanson, K.L., O’Dwyer, P.J., Flaherty, K.T.: 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. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8527 (2007)

    Google Scholar 

  3. Atkins, M.B., Hsu, J., Lee, S., Cohen, G.I., Flaherty, L.E., Sosman, J.A., Sondak, V.K., Kirkwood, J.M.: 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 26, 5748–5754 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. Atkins, M.B., Lotze, M.T., Dutcher, J.P., Fisher, R.I., Weiss, G., Margolin, K., Abrams, J., Sznol, M., Parkinson, D., Hawkins, M., Paradise, C., Kunkel, L., Rosenberg, S.A.: High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17, 2105–2116 (1999)

    CAS  PubMed  Google Scholar 

  5. Atkins, M.B.: Cytokine-based therapy and biochemotherapy for advanced melanoma. Clin Cancer Res 12, 2353s–2358s (2006)

    Article  CAS  PubMed  Google Scholar 

  6. Attia, P., Phan, G.Q., Maker, A.V., Robinson, M.R., Quezado, M.M., Yang, J.C., Sherry, R.M., Topalian, S.L., Kammula, U.S., Royal, R.E., Restifo, N.P., Haworth, L.R., Levy, C., Mavroukakis, S.A., Nichol, G., Yellin, M.J., Rosenberg, S.A.: Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 23, 6043–6053 (2005)

    Article  CAS  PubMed  Google Scholar 

  7. Avril, M.F., Aamdal, S., Grob, J.J., Hauschild, A., Mohr, P., Bonerandi, J.J., Weichenthal, M., Neuber, K., Bieber, T., Gilde, K., Guillem Porta, V., Fra, J., Bonneterre, J., Saïag, P., Kamanabrou, D., Pehamberger, H., Sufliarsky, J., Gonzalez Larriba, J.L., Scherrer, A., Menu, Y.: Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 22, 1118–1125 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. Bajetta, E., Di Leo, A., Zampino, M.G., Sertoli, M.R., Comella, G., Barduagni, M., Giannotti, B., Queirolo, P., Tribbia, G., Bernengo, M.G.: Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. J Clin Oncol 12, 806–811 (1994)

    CAS  PubMed  Google Scholar 

  9. Bedikian, A.Y., Millward, M., Pehamberger, H., Conry, R., Gore, M., Trefzer, U., Pavlick, A.C., DeConti, R., Hersh, E.M., Hersey, P., Kirkwood, J.M., Haluska, F.G.: Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 24, 4738–4745 (2006)

    Article  CAS  PubMed  Google Scholar 

  10. Bleehen, N.M., Newlands, E.S., Lee, S.M., Thatcher, N., Selby, P., Calvert, A.H., Rustin, G.J., Brampton, M., Stevens, M.F.: Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 13, 910–913 (1995)

    CAS  PubMed  Google Scholar 

  11. Bong, A.B., Bonnekoh, B., Franke, I., Schon, M.P., Ulrich, J., Gollnick, H.: Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology 205, 135–138 (2002)

    Article  CAS  PubMed  Google Scholar 

  12. Cameron, D.A., Cornbleet, M.C., Mackie, R.M., Hunter, J.A., Gore, M., Hancock, B., Smyth, J.F.: Adjuvant interferon alpha 2b in high risk melanoma – the Scottish study. Br J Cancer 84, 1146–1149 (2001)

    Article  CAS  PubMed  Google Scholar 

  13. Carmichael, J., Atkinson, R.J., Calman, K.C., Mackie, R.M., Naysmith, A.M., Smyth, J.F.: A multicentre phase II trial of vindesine in malignant melanoma. Eur J Cancer Clin Oncol 18, 1293–1295 (1982)

    Article  CAS  PubMed  Google Scholar 

  14. Carter, R.D., Krementz, E.T., Hill, G.J., Metter, G.E., Fletcher, W.S., Golomb, F.M., Grage, T.B., Minton, J.P., Sparks, F.C.: DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065). Cancer Treat Rep 60, 601–609 (1976)

    CAS  PubMed  Google Scholar 

  15. Cascinelli, N., Belli, F., Mackie, R.M., 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 358, 866–869 (2001)

    Article  CAS  PubMed  Google Scholar 

  16. Chapman, P.B., Einhorn, L.H., Meyers, M.L., Saxman, S., Destro, A.N., Panageas, K.S., Begg, C.B., Agarwala, S.S., Schuchter, L.M., Ernstoff, M.S., Houghton, A.N., Kirkwood, J.M.: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17, 2745–2751 (1999)

    CAS  PubMed  Google Scholar 

  17. Chiarion-Sileni, V., Nortilli, R., Aversa, S.M., Paccagnella, A., Medici, M., Corti, L., Favaretto, A.G., Cetto, G.L., Monfardini, S.: Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients. Melanoma Res 11, 189–196 (2001)

    Article  CAS  PubMed  Google Scholar 

  18. Chiarion-Sileni, V., Del Bianco, P., Romanini, A., Guida, M., Paccagnella, A., Dalla, P.M., Naglieri, E., Ridolfi, R., Silvestri, B., Michiara, M., De Salvo, G.L.: 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 (IMI - Mel.A.) [ISRCTN75125874]. BMC Cancer 6, 44 (2006)

    Article  PubMed  CAS  Google Scholar 

  19. Cornett, W.R., McCall, L.M., Petersen, R.P., Ross, M.I., Briele, H.A., Noyes, R.D., Sussman, J.J., Kraybill, W.G., Kane, J.M.I., Alexander, H.R., Lee, J.E., Mansfield, P.F., Pingpank, J.F., Winchester, D.J., RLJr, W., Chadaram, V., Herndon, J.E., Fraker, D.L., Tyler, D.S.: Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. J Clin Oncol 24, 4196–4201 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. Costanzi, J.J., Al Sarraf, M., Groppe, C., Bottomley, R., Fabian, C., Neidhart, J., Dixon, D.: Combination chemotherapy plus BCG in the treatment of disseminated malignant melanoma: a Southwest Oncology Group Study. Med Pediatr Oncol 10, 251–258 (1982)

    Article  CAS  PubMed  Google Scholar 

  21. Creagan, E.T., Ahmann, D.L., Frytak, S., Long, H.J., Chang, M.N., Itri, L.M.: Three consecutive phase II studies of recombinant interferon alfa-2a in advanced malignant melanoma. Updated analyses. Cancer 59, 638–646 (1987)

    Article  CAS  PubMed  Google Scholar 

  22. Creagan, E.T., Dalton, R.J., Ahmann, D.L., Jung, S.H., Morton, R.F., Langdon Jr., R.M., Kugler, J., Rodrigue, L.J.: Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol 13, 2776–2783 (1995)

    CAS  PubMed  Google Scholar 

  23. Creagan, E.T., Suman, V.J., Dalton, R.J., Pitot, H.C., Long, H.J., Veeder, M.H., Vukov, A.M., Rowland, K.M., Krook, J.E., Michalak, J.C.: Phase III clinical trial of the combination of cisplatin, dacarbazine, and carmustine with or without tamoxifen in patients with advanced malignant melanoma. J Clin Oncol 17, 1884–1890 (1999)

    CAS  PubMed  Google Scholar 

  24. Davies, B.R., Logie, A., McKay, J.S., Martin, P., Steele, S., Jenkins, R., Cockerill, M., Cartlidge, S., Smith, P.D.: AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular 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 6, 2209–2219 (2007)

    Article  CAS  PubMed  Google Scholar 

  25. Dorval, T., Mathiot, C., Chosidow, O., Revuz, J., Avril, M.F., Guillaume, J.C., Tursz, T., Brandely, M., Pouillart, P., Fridman, W.H.: IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters. Biotechnol Ther 3, 63–79 (1992)

    CAS  PubMed  Google Scholar 

  26. Egerer, G., Lehnert, T., Max, R., Naeher, H., Keilholz, U., Ho, A.D.: Pilot study of hepatic intraarterial fotemustine chemotherapy for liver metastases from uveal melanoma: a single-center experience with seven patients. Int J Clin Oncol 6, 25–28 (2001)

    Article  CAS  PubMed  Google Scholar 

  27. Eggermont, A., Suciu, S., Ruka, W., Mardsen, J., Testori, A., Corrie, P.G., Aamdal, S., Ascierto, P., Patel, P., Spatz, A.: EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results. J. Clin. Oncol. 26, abstract 9004 (2008)

    Google Scholar 

  28. Eggermont, A.M., Kirkwood, J.M.: Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years? Eur J Cancer 40, 1825–1836 (2004)

    Article  CAS  PubMed  Google Scholar 

  29. Eggermont, A.M., Suciu, S., Santinami, M., Testori, A., Kruit, W.H., Marsden, J., Punt, C.J., Sales, F., Gore, M., Mackie, R., Kusic, Z., Dummer, R., Hauschild, A., Musat, E., Spatz, A., Keilholz, U.: 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 372, 117–126 (2008)

    Article  CAS  PubMed  Google Scholar 

  30. Eggermont, A.M.M., Suciu, S., MacKie, R., Ruka, W., Testori, A., Kruit, W., Punt, C.J.A., Delauney, M., Fo, S., Groenewegen, G., Ruiter, D.J., Jagiello, I., Stoitchkov, K., Keilholz, U., Lienard, D.: 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 366, 1189–1196 (2005)

    Article  CAS  PubMed  Google Scholar 

  31. Eigentler, T.K., Caroli, U.M., Radny, P., Garbe, C.: Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 4, 748–759 (2003)

    Article  CAS  PubMed  Google Scholar 

  32. Eisen, T., Ahmad, T., Flaherty, K.T., Gore, M., Kaye, S., Marais, R., Gibbens, I., Hackett, S., James, M., Schuchter, L.M., Nathanson, K.L., Xia, C., Simantov, R., Schwartz, B., Poulin-Costello, M., O’Dwyer, P.J., Ratain, M.J.: Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis. Br J Cancer 95, 581–586 (2006)

    Article  CAS  PubMed  Google Scholar 

  33. Falkson, C.I., Ibrahim, J., Kirkwood, J.M., Coates, A.S., Atkins, M.B., Blum, R.H.: Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 16, 1743–1751 (1998)

    CAS  PubMed  Google Scholar 

  34. Faries, M.B., Morton, D.L.: Therapeutic vaccines for melanoma: current status. Biodrugs 19, 247–260 (2005)

    Article  CAS  PubMed  Google Scholar 

  35. Flaherty, K.T.: Chemotherapy and targeted therapy combinations in advanced melanoma. Clin Cancer Res 12, 2366s–2370s (2006)

    Article  CAS  PubMed  Google Scholar 

  36. Flaherty, K.T., Brose, M.S., Schuchter, L.M., Tuveson, D., Lee, R., Schwartz, B., Lathia, C., Weber, B.L., O’Dwyer, P.J.: Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. J. Clin. Oncol. 22, ASCO Annual Meeting Proceedings (Post-Meeting Edition)-Abstract No: 7507 (2004)

    Google Scholar 

  37. Garaci, E.: Thymosin alpha1: a historical overview. Ann N Y Acad Sci 1112, 14–20 (2007)

    Article  CAS  PubMed  Google Scholar 

  38. Garbe, C., Radny, P., Linse, R., Dummer, R., Gutzmer, R., Ulrich, J., Stadler, R., Weichenthal, M., Eigentler, T., Ellwanger, U., Hauschild, A.: Adjuvant low-dose interferon {alpha}2a 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 19, 1195–1201 (2008)

    Article  CAS  PubMed  Google Scholar 

  39. Garbe, C., Eigentler, T.K.: Diagnosis and treatment of cutaneous melanoma: state of the art 2006. Melanoma Res 17, 117–127 (2007)

    Article  PubMed  Google Scholar 

  40. Gimbel, M.I., Delman, K.A., Zager, J.S.: Therapy for unresectable recurrent and in-transit extremity melanoma. Cancer Control 15, 225–232 (2008)

    PubMed  Google Scholar 

  41. Gomez-Navarro, J., Antonia, S., Sosman, J.A., Kirkwood, J.M., Redman, B., Gajewski, T.F., Pavlov, D., Bulanhagui, C.A., Ribas, A., Camacho, L.H.: 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. 25, ASCO Annual Meeting Proceedings Part I. Abstract No: 8524 (2007)

    Google Scholar 

  42. Gonzalez, R., Hutchins, L., Nemunaitis, J., Atkins, M., Schwarzenberger, P.O.: Phase 2 trial of Allovectin-7 in advanced metastatic melanoma. Melanoma Res 16, 521–526 (2006)

    Article  CAS  PubMed  Google Scholar 

  43. Green, D.S., Bodman-Smith, M.D., Dalgleish, A.G., Fischer, M.D.: Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol 156, 337–345 (2007)

    Article  CAS  PubMed  Google Scholar 

  44. Grob, J.J., Dreno, B., de la Salmonière, P., Delaunay, M., Cupissol, D., Guillot, B., Souteyrand, P., Sassolas, B., Cesarini, J.P., Lionnet, S., Lok, C., Chastang, C., Bonerandi, J.J.: Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet 351, 1905–1910 (1998)

    Article  CAS  PubMed  Google Scholar 

  45. Gundersen, S.: Dacarbazine, vindesine, and cisplatin combination chemotherapy in advanced malignant melanoma: a phase II study. Cancer Treat Rep 71, 997–999 (1987)

    CAS  PubMed  Google Scholar 

  46. Hamid, O., Urba, W., Yellin, M., Nichol, G., Weber, J.S., Hersh, E.M., Tchekmedyian, S., Hodi, F.S., Weber, S., O’Day, S.J.: Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma. J. Clin. Oncol. 25, ASCO annual meeting proceedings part i-abstract no: 8525 (2007)

    Google Scholar 

  47. Hancock, B.W., Wheatley, K., Harris, S., Ives, N., Harrison, G., Horsman, J.M., Middleton, M.R., Thatcher, N., Lorigan, P.C., Marsden, J.R., Burrows, L., Gore, M.: 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 22, 53–61 (2004)

    Article  CAS  PubMed  Google Scholar 

  48. Hayes, A.J., Clark, M.A., Harries, M., Thomas, J.M.: Management of in-transit metastases from cutaneous malignant melanoma. Br J Surg 91, 673–682 (2004)

    Article  CAS  PubMed  Google Scholar 

  49. Hersey, P.: Adjuvant therapy for high-risk primary and resected metastatic melanoma. Intern Med J 33, 33–43 (2003)

    Article  CAS  PubMed  Google Scholar 

  50. Ives, N.J., Stowe, R.L., Lorigan, P., Wheatley, K.: Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol 25, 5426–5434 (2007)

    Article  CAS  PubMed  Google Scholar 

  51. Jacquillat, C., Khayat, D., Banzet, P., Weil, M., Fumoleau, P., Avril, M.F., Namer, M., Bonneterre, J., Kerbrat, P., Bonerandi, J.J.: Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. Cancer 66, 1873–1878 (1990)

    Article  CAS  PubMed  Google Scholar 

  52. Jones, E.L., Oleson, J.R., Prosnitz, L.R., Samulski, T.V., Vujaskovic, Z., Yu, D., Sanders, L.L., Dewhirst, M.W.: Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol 23, 3079–3085 (2005)

    Article  PubMed  Google Scholar 

  53. Jungnelius, U., Ringborg, U., Aamdal, S., Mattsson, J., Stierner, U., Ingvar, C., Malmstrom, P., Andersson, R., Karlsson, M., Willman, K., Wist, E., Bjelkengren, G., Westberg, R.: Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A randomised phase III trial. Eur J Cancer 34, 1368–1374 (1998)

    Article  CAS  PubMed  Google Scholar 

  54. Kamin, A., Eigentler, T.K., Radny, P., Bauer, J., Weide, B., Garbe, C.: Imiquimod in the treatment of extensive recurrent lentigo maligna. J Am Acad Dermatol 52, 51–52 (2005)

    Article  PubMed  Google Scholar 

  55. Kaufmann, R., Spieth, K., Leiter, U., Mauch, C., von den, D.P., Vogt, T., Linse, R., Tilgen, W., Schadendorf, D., Becker, J.C., Sebastian, G., Krengel, S., Kretschmer, L., Garbe, C., Dummer, R.: 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 23, 9001–9007 (2005)

    Article  CAS  PubMed  Google Scholar 

  56. Kavanagh, D., Hill, A.D.K., Djikstra, B., Kennelly, R., McDermott, E.M.W., O’Higgins, N.J.: Adjuvant therapies in the treatment of stage II and III malignant melanoma. Surgeon 3, 245–256 (2005)

    Article  CAS  PubMed  Google Scholar 

  57. Keilholz, U., Stoter, G., Punt, C.J., Scheibenbogen, C., Lejeune, F., Eggermont, A.M.: 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 3(suppl 1), S22–S28 (1997)

    PubMed  Google Scholar 

  58. Keilholz, U., Punt, C.J.A., Gore, M., Kruit, W., Patel, P., Lienard, D., Thomas, J., Proebstle, T.M., Schmittel, A., Schadendorf, D., Velu, T., Negrier, S., Kleeberg, U., Lehman, F., Suciu, S., Eggermont, A.M.M.: 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 23, 6747–6755 (2005)

    Article  CAS  PubMed  Google Scholar 

  59. Kim, C.J., Dessureault, S., Gabrilovich, D., Reintgen, D.S., Slingluff, C.L.: Immunotherapy for melanoma. Cancer Control 9, 22–30 (2002)

    PubMed  Google Scholar 

  60. Kim, K.B., Legha, S.S., Gonzalez, R., Anderson, C., Papadopoulos, N.E., Eton, O., Plager, C., Roe, A., Liu, P., Bedikian, A.Y.: A phase III randomized trial of adjuvant biochemotherapy (BC) versus interferon-alpha-2b (IFN) in patients (pts) with high risk for melanoma recurrence. J. Clin. Oncol. 24, 8003 (2006)

    Google Scholar 

  61. Kirkwood, J.M., Ibrahim, J.G., Sondak, V.K., Richards, J., Flaherty, L.E., Ernstoff, M.S., Smith, T.J., Rao, U., Steele, M., Blum, R.H.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 18, 2444–2458 (2000)

    CAS  PubMed  Google Scholar 

  62. Kirkwood, J.M., Ibrahim, J.G., Sosman, J.A., Sondak, V.K., Agarwala, S.S., Ernstoff, M.S., Rao, U.: 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 19, 2370–2380 (2001)

    CAS  PubMed  Google Scholar 

  63. Kirkwood, J.M., Strawderman, M.H., Ernstoff, M.S., Smith, T.J., Borden, E.C., Blum, R.H.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14, 7–17 (1996)

    CAS  PubMed  Google Scholar 

  64. Kirkwood, J.M., Bender, C., Agarwala, S., Tarhini, A., Shipe-Spotloe, J., Smelko, B., Donnelly, S., Stover, L.: Mechanisms and management of toxicities associated with high-dose interferon alfa-2b therapy. J Clin Oncol 20, 3703–3718 (2002)

    Article  CAS  PubMed  Google Scholar 

  65. Knutson, K.L.: GMK (Progenics Pharmaceuticals). Curr Opin Investig Drugs 3, 159–164 (2002)

    CAS  PubMed  Google Scholar 

  66. Legha, S.S., Gianan, M.A., Plager, C., Eton, O.E., Papadopoulous, N.E.: Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma. Cancer 77, 89–96 (1996)

    Article  CAS  PubMed  Google Scholar 

  67. Lens, M.B., Dawes, M.: Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 20, 1818–1825 (2002)

    Article  CAS  PubMed  Google Scholar 

  68. Lens, M.B., Eisen, T.G.: Systemic chemotherapy in the treatment of malignant melanoma. Expert Opin Pharmacother 4, 2205–2211 (2003)

    Article  CAS  PubMed  Google Scholar 

  69. Leyvraz, S., Spataro, V., Bauer, J., Pampallona, S., Salmon, R., Dorval, T., Meuli, R., Gillet, M., Lejeune, F., Zografos, L.: Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol 15, 2589–2595 (1997)

    CAS  PubMed  Google Scholar 

  70. Malek-Mansour, S.: Remission of melanoma with D.N.C.B. treatment. Lancet 2, 503–504 (1973)

    Article  CAS  PubMed  Google Scholar 

  71. McClay, E.F., Mastrangelo, M.J., Bellet, R.E., Berd, D.: Combination chemotherapy and hormonal therapy in the treatment of malignant melanoma. Cancer Treat Rep 71, 465–469 (1987)

    CAS  PubMed  Google Scholar 

  72. McDermott, E.M.W., Sosman, J.A., Hodi, F.S., Gonzalez, R., Linette, G., Richards, J., Jakub, J.K., Beerem, M., Patel, K., Kramner, C.: Randomized phase II study of dacarbazine with or without sorafenib in patients with advanced melanoma. J. Clin. Oncol. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8511 (2007)

    Google Scholar 

  73. Middleton, M.R., Grob, J.J., Aaronson, N., Fierlbeck, G., Tilgen, W., Seiter, S., Gore, M., Aamdal, S., Cebon, J., Coates, A., Dreno, B., Henz, M., Schadendorf, D., Kapp, A., Weiss, J., Fraass, U., Statkevich, P., Muller, M., Thatcher, N.: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18, 158–166 (2000)

    CAS  PubMed  Google Scholar 

  74. Miller, R.L., Steis, R.G., Clark, J.W., Smith, J.W., Crum, E., McKnight, J.E., Hawkins, M.J., Jones, M.J., Longo, D.L., Urba, W.J.: Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Res 49, 1871–1876 (1989)

    CAS  PubMed  Google Scholar 

  75. Millward, M., Bedikian, A.Y., Conry, R,. Gore, M., Pehamberger, H., Sterry, W., Pavlick, A., De Conti, R., Gordon, D., Itri, L.M.: Randomized multinational phase 3 trial of dacarbazine (DTIC) with or without Bcl-2 antisense (oblimersen sodium) in patients (pts) with advanced malignant melanoma (MM): Analysis of long-term survival. J. Clin. Oncol. 22, ASCO Annual Meeting Proceedings (Post-Meeting Edition)-Abstract No: 7505 (2004)

    Google Scholar 

  76. Mornex, F., Thomas, L., Mohr, P., Hauschild, A., Delaunay, M.M., Lesimple, T., Tilgen, W., Bui, B.N., Guillot, B., Ulrich, J., Bourdin, S., Mousseau, M., Cupissol, D., Bonneterre, M.E., De Gislain, C., Bensadoun, R.J., Clavel, M.: A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res 13, 97–103 (2003)

    Article  CAS  PubMed  Google Scholar 

  77. Morton, D., Mozzillo, N., Thompson, J.A., Kelly, M., Faries, M., Wagner, J., Schneebaum, S., Schuchter, L., Gammon, G., Elashoff, R.: 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. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8508 (2007)

    Google Scholar 

  78. Naylor, M.F., Crowson, N., Kuwahara, R., Teague, K., Garcia, C., Mackinnis, C., Haque, R., Odom, C., Jankey, C., Cornelison, R.L.: Treatment of lentigo maligna with topical imiquimod. Br J Dermatol 149, 66–70 (2003)

    Article  CAS  PubMed  Google Scholar 

  79. Neefe, J.R., Legha, S.S., Markowitz, A., Salmon, S., Meyskens, F., Groopman, J., Campion, M., Evans, L.: Phase II study of recombinant alpha-interferon in malignant melanoma. Am J Clin Oncol 13, 472–476 (1990)

    Article  CAS  PubMed  Google Scholar 

  80. Nelimark, R.A., Peterson, B.A., Vosika, G.J., Conroy, J.A.: Vindesine for metastatic malignant melanoma. A phase II trial. Am J Clin Oncol 6, 561–564 (1983)

    CAS  PubMed  Google Scholar 

  81. O’Day, S.J., Hamid, O., Urba, W.J.: Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer 110, 2614–2627 (2007)

    Article  PubMed  CAS  Google Scholar 

  82. O’Day, S.J., Gonzalez, R., Lawson, L., Weber, R., Hutchins, L., Anderson, C., McLeod, M., Hurwitz, C., Haddad, J., Jacobson, E.: Subgroup analysis of efficacy and safety analysis of a randomized, double-blinded controlled phase II study of STA-4783 in combination with paclitaxel in patients with metastatic melanoma. J. Clin. Oncol. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8528 (2007)

    Google Scholar 

  83. Pectasides, D., Alevizakos, N., Bafaloukos, D., Tzonou, A., Asimakopoulos, G., Varthalitis, I., Dimitriadis, M., Athanassiou, A.: Adjuvant chemotherapy with dacarbazine, vindesine, and cisplatin in pathological stage II malignant melanoma. Am J Clin Oncol 17, 55–59 (1994)

    Article  CAS  PubMed  Google Scholar 

  84. Pehamberger, H., Soyer, H.P., Steiner, A., Kofler, R., Binder, M., Mischer, P., Pachinger, W., Aubock, J., Fritsch, P., Kerl, H., Wolff, K.: Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol 16, 1425–1429 (1998)

    CAS  PubMed  Google Scholar 

  85. Pföhler, C., Cree, I.A., Ugurel, S., Kuwert, C., Haass, N., Neuber, K., Hengge, U., Corrie, P.G., Zutt, M., Tilgen, W., Reinhold, U.: Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study. Anticancer Drugs 14, 337–340 (2003)

    Article  PubMed  Google Scholar 

  86. Powell, A.M., Russell-Jones, R., Barlow, R.J.: Topical imiquimod immunotherapy in the management of lentigo maligna. Clin Exp Dermatol 29, 15–21 (2004)

    Article  CAS  PubMed  Google Scholar 

  87. Prins, R.M., Craft, N., Bruhn, K.W., Khan-Farooqi, H., Koya, R.C., Stripecke, R., Miller, J.F., Liau, L.M.: The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity. J Immunol 176, 157–164 (2006)

    CAS  PubMed  Google Scholar 

  88. Quaglino, P., Mortera, C., Osella-Abate, S., Barberis, M., Illengo, M., Rissone, M., Savoia, P., Bernengo, M.G.: Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol 15, 2215–2222 (2008)

    Article  CAS  PubMed  Google Scholar 

  89. Radny, P., Caroli, U.M., Bauer, J., Paul, T., Schlegel, C., Eigentler, T.K., Weide, B., Schwarz, M., Garbe, C.: Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer 89, 1620–1626 (2003)

    Article  CAS  PubMed  Google Scholar 

  90. Rao, R.D., Holtan, S.G., Ingle, J.N., Croghan, G.A., Kottschade, L.A., Creagan, E.T., Kaur, J.S., Pitot, H.C., Markovic, S.N.: Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma. Cancer 106, 375–382 (2006)

    Article  CAS  PubMed  Google Scholar 

  91. Rasi, G., Terzoli, E., Izzo, F., Pierimarchi, P., Ranuzzi, M., Sinibaldi-Vallebona, P., Tuthill, C., Garaci, E.: Combined treatment with thymosin-alpha1 and low dose interferon-alpha after dacarbazine in advanced melanoma. Melanoma Res 10, 189–192 (2000)

    CAS  PubMed  Google Scholar 

  92. Ribas, A.: Update on immunotherapy for melanoma. J Natl Compr Canc Netw 4, 687–694 (2006)

    CAS  PubMed  Google Scholar 

  93. Ribas, A., Antonia, S., Sosman, J.A., Kirkwood, J.M., Redman, B., Gajewski, T.F., Pavlov, D., Bulanhagui, C.A., Gomez-Navarro, J., Camacho, L.H.: Results of a phase II clinical trial of 2 doses and schedules of CP-675,206, an anti-CTLA4 monoclonal antibody, in patients (pts) with advanced melanoma. J. Clin. Oncol. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 3000 (2007)

    Google Scholar 

  94. Ribas, A., Hanson, D.C., Noe, D.A., Millham, R., Guyot, D.J., Bernstein, S.H., Canniff, P.C., Sharma, A., Gomez-Navarro, J.: Tremelimumab (CP-675, 206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer. Oncologist 12, 873–883 (2007)

    Article  CAS  PubMed  Google Scholar 

  95. Ringborg, U., Rudenstam, C.M., Hansson, J., Hafstrom, L., Stenstam, B., Strander, H.: Dacarbazine versus dacarbazine-vindesine in disseminated malignant melanoma: a randomized phase II study. Med Oncol Tumor Pharmacother 6, 285–289 (1989)

    CAS  PubMed  Google Scholar 

  96. Robinson, W.A., Mughal, T.I., Thomas, M.R., Johnson, M., Spiegel, R.J.: Treatment of metastatic malignant melanoma with recombinant interferon alpha 2. Immunobiology 172, 275–282 (1986)

    Article  CAS  PubMed  Google Scholar 

  97. Satyamoorthy, K., Li, G., Gerrero, M.R., Brose, M.S., Volpe, P., Weber, B.L., Van Belle, P., Elder, D.E., Herlyn, M.: Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res 63, 756–759 (2003)

    CAS  PubMed  Google Scholar 

  98. Schadendorf, D., Ugurel, S., Schuler-Thurner, B., Nestle, F.O., Enk, A., Bröcker, E.B., Grabbe, S., Rittgen, W., Edler, L., Sucker, A., Zimpfer-Rechner, C., Berger, T., Kamarashev, J., Burg, G., Jonuleit, H., Tuttenberg, A., Becker, J.C., Keikavoussi, P., Kämpgen, E., Schuler, G.: Dacarbazine (DTIC) versus vaccination with autologous 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 17, 563–570 (2006)

    Article  CAS  PubMed  Google Scholar 

  99. Seegenschmiedt, M.H., Keilholz, L., Altendorf-Hofmann, A., Urban, A., Schell, H., Hohenberger, W., Sauer, R.: Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience. Int J Radiat Oncol Biol Phys 44, 607–618 (1999)

    Article  CAS  PubMed  Google Scholar 

  100. Seigler, H.F., Lucas Jr., V.S., Pickett, N.J., Huang, A.T.: DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma. Cancer 46, 2346–2348 (1980)

    Article  CAS  PubMed  Google Scholar 

  101. Senzer, N.N., Kaufman, H.L., Amatruda, T.T., Nemunaitis, M., Reid, T.R., Love, C., Marshall, T., Goldsweig, H., Coffin, R.S., Nemunaitis, J.: Phase II clinical trial with a second generation, GM-CSF encoding, oncolytic herpesvirus in unresectable metastatic melanoma. J. Clin. Oncol. 26(suppl), Abstract No: 9008 (2008)

    Google Scholar 

  102. Siegel, R., Hauschild, A., Kettelhack, C., Kahler, K.C., Bembenek, A., Schlag, P.M.: Hepatic arterial Fotemustine chemotherapy in patients with liver metastases from cutaneous melanoma is as effective as in ocular melanoma. Eur J Surg Oncol 33, 627–632 (2007)

    Article  CAS  PubMed  Google Scholar 

  103. Smith, K.A., Green, J.A., Eccles, J.M.: Interferon alpha 2a and vindesine in the treatment of advanced malignant melanoma. Eur J Cancer 28, 438–441 (1992)

    Article  CAS  PubMed  Google Scholar 

  104. Sondak, V.K.: Adjuvant therapy for melanoma. Cancer J 7(suppl 1), S24–S27 (2001)

    PubMed  Google Scholar 

  105. Stadler, R., Luger, T., Bieber, T., Köhler, U., Linse, R., Technau, K., Schubert, R., Schroth, K., Vakilzadeh, F., Volkenandt, M., Gollnick, H., Von Eick, H., Thoren, F., Strannegård, O.: Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial. Acta Oncol 45, 389–399 (2006)

    Article  CAS  PubMed  Google Scholar 

  106. Tarhini, A.A., Kirkwood, J.M.: Oblimersen in the treatment of metastatic melanoma. Future Oncol 3, 263–271 (2007)

    Article  CAS  PubMed  Google Scholar 

  107. Terheyden, P., Kortum, A.K., Schulze, H.J., Durani, B., Remling, R., Mauch, C., Junghans, V., Schadendorf, D., Beiteke, U., Junger, M., Becker, J.C., Bröcker, E.B.: Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group. J Cancer Res Clin Oncol 133, 437–444 (2007)

    Article  CAS  PubMed  Google Scholar 

  108. Thompson, J.F., Kam, P.C., Waugh, R.C., Harman, C.R.: Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol 14, 238–247 (1998)

    Article  CAS  PubMed  Google Scholar 

  109. Verschraegen, C.F., Kleeberg, U.R., Mulder, J., Rumke, P., Truchetet, F., Czarnetzki, B., Rozencweig, M., Thomas, D., Suciu, S.: Combination of cisplatin, vindesine, and dacarbazine in advanced malignant melanoma. A Phase II Study of the EORTC Malignant Melanoma Cooperative Group. Cancer 62, 1061–1065 (1988)

    Article  CAS  PubMed  Google Scholar 

  110. Wack, C., Kirst, A., Becker, J.C., Lutz, W.K., Brocker, E.B., Fischer, W.H.: Chemoimmunotherapy for melanoma with dacarbazine and 2, 4-dinitrochlorobenzene elicits a specific T cell-dependent immune response. Cancer Immunol Immunother 51, 431–439 (2002)

    Article  CAS  PubMed  Google Scholar 

  111. Weber, J.S., Hersh, E.M., Yellin, M., Nichol, G., Urba, W., Powderly, W., O’Day, S.J.: The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma. J. Clin. Oncol. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8523 (2007)

    Google Scholar 

  112. Wheatley, K., Ives, N., Eggermont, A.: Interferon-alpha as adjuvant therapy for melanoma: An individual patient data meta-analysis of randomised trials. J. Clin. Oncol. 25, ASCO Annual Meeting Proceedings Part I-Abstract No: 8526 (2007)

    Google Scholar 

  113. 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 29, 241–252 (2003)

    Article  CAS  PubMed  Google Scholar 

  114. Wolf, I.H., Richtig, E., Kopera, D., Kerl, H.: Locoregional cutaneous metastases of malignant melanoma and their management. Dermatol Surg 30, 244–247 (2004)

    Article  PubMed  Google Scholar 

  115. Wolf, I.H., Smolle, J., Binder, B., Cerroni, L., Richtig, E., Kerl, H.: Topical imiquimod in the treatment of metastatic melanoma to skin. Arch Dermatol 139, 273–276 (2003)

    Article  PubMed  Google Scholar 

  116. York, R.M., Foltz, A.T.: Bleomycin, vincristine, lomustine, and DTIC chemotherapy for metastatic melanoma. Cancer 61, 2183–2186 (1988)

    Article  CAS  PubMed  Google Scholar 

  117. Young, A.M., Marsden, J., Goodman, A., Burton, A., Dunn, J.A.: Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma. Clin Oncol (R Coll Radiol ) 13, 458–465 (2001)

    CAS  Google Scholar 

  118. Zarour, H.M., Kirkwood, J.M.: Melanoma vaccines: early progress and future promises. Semin Cutan Med Surg 22, 68–75 (2003)

    Article  PubMed  Google Scholar 

Adjuvant Immunotherapy in Melanoma: Pegylated Interferons: A New Perspective

  1. Isaacs, A., Lindenmann, J.: Virus Interference. I The interferon. Proc R Soc London Ser B 147, 258 (1957)

    Article  CAS  Google Scholar 

  2. Kerr, I.M., Stark, G.R.: The antiviral effects of the interferons and their inhibition. J Interferon Res 12, 237–240 (1992)

    Article  CAS  PubMed  Google Scholar 

  3. Samuel, C.E.: Antiviral actions of interferons. Clin Microbiol Rev 14, 778–809 (2001)

    Article  CAS  PubMed  Google Scholar 

  4. Sen, G.C., Lengyel, P.: The interferon system. A bird’s eye view of its biochemistry. J Biol Chem 267, 5017–5020 (1992)

    CAS  PubMed  Google Scholar 

  5. Nathan, C.: Interferon and inflammation. In: Gallin, J.I., Goldstein, I.M., Schnyder, R. (eds.) Inflammation: Basic Principles and Clinical Correlates, pp. 265–290. Raven, New York (1992)

    Google Scholar 

  6. Beattie, E., Tartaglia, J.: PaolettiE: Vaccinia virus-encoded elF-2a homolog abbrogates the anitiviral effect of interferon. Virology 183, 419–422 (1991)

    Article  CAS  PubMed  Google Scholar 

  7. Bandyopadhyay, S., Perussia, B., Trinchieri, G., et al.: Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts. J Exp Med 164, 180–195 (1986)

    Article  CAS  PubMed  Google Scholar 

  8. Siegal, F.P., Kadowaki, N., Shodell, M., et al.: The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835–1837 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. Cella, M., Jarrossay, D., Facchetti, F., et al.: Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5, 919–923 (1999)

    Article  CAS  PubMed  Google Scholar 

  10. Colonna, M., Trinchieri, G., Liu, Y.J.: Plasmacytoid dendritic cells in immunity. Nat Immunol 5, 1219–1226 (2004)

    Article  CAS  PubMed  Google Scholar 

  11. McKenna, K., Beignon, A.S., Bhardwaj, N.: Plasmacytoid dendritic cells: linking innate and adaptive immunity. J Virol 79, 17–27 (2005)

    Article  CAS  PubMed  Google Scholar 

  12. Iwasaki, A., Medzhitov, R.: Toll-like receptor control of the adaptive immune responses. Nat Immunol 5, 987–995 (2004)

    Article  CAS  PubMed  Google Scholar 

  13. Bell, D., Chomarat, P., Broyles, D., et al.: In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 190, 1417–1426 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. Vermi, W., Bonecchi, R., Facchetti, F., et al.: Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas. J Pathol 200, 255–268 (2003)

    Article  PubMed  Google Scholar 

  15. Liu, C., Lou, Y., Lizee, G., et al.: Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest 118, 1165–1175 (2008)

    CAS  PubMed  Google Scholar 

  16. Pestka, S., Langer, J.A., Zoon, K.C., et al.: Interferons and their actions. Annu Rev Biochem 56, 727–777 (1987)

    Article  CAS  PubMed  Google Scholar 

  17. Kaplan, D.H., Shankaran, V., Dighe, A.S., et al.: Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A 95, 7556–7561 (1998)

    Article  CAS  PubMed  Google Scholar 

  18. Dunn, G.P., Bruce, A.T., Sheehan, K.C., et al.: A critical function for type I interferons in cancer immunoediting. Nat Immunol 6, 722–729 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. Paredes, J., Krown, S.E.: Interferon-alpha therapy in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome. Int J Immunopharmacol 13(suppl 1), 77–81 (1991)

    Article  PubMed  Google Scholar 

  20. Baron, S., Tyring, S.K., Fleischmann Jr., W.R., et al.: The interferons. Mechanisms of action and clinical applications. JAMA 266, 1375–1383 (1991)

    Article  CAS  PubMed  Google Scholar 

  21. Borden, E.C.: Interferons. In: Holland, J.F., Frei, I.I.I., Bast, J.R., Kufe, D.W., Morton, D.L., Wechselbaum, R.R. (eds.) Cancer Medicine, pp. 1119–1212. Lippincott Wiliams & Wilkins, Philadelphia (1997)

    Google Scholar 

  22. Gutterman, J.U.: Cytokine therapeutics: lessons from interferon alpha. Proc Natl Acad Sci U S A 91, 1198–1205 (1994)

    Article  CAS  PubMed  Google Scholar 

  23. Buzaid, A.C., Robertone, A., Kisala, C., et al.: Phase II study of interferon alfa-2a, recombinant (Roferon-A) in metastatic renal cell carcinoma. J Clin Oncol 5, 1083–1089 (1987)

    CAS  PubMed  Google Scholar 

  24. Krown, S.E.: Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer 59, 647–651 (1987)

    Article  CAS  PubMed  Google Scholar 

  25. Interferon nomenclature. Nature 286, 110 (1980)

    Google Scholar 

  26. Platanias, L.C.: Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5, 375–386 (2005)

    Article  CAS  PubMed  Google Scholar 

  27. Pestka, S.: The human interferon-alpha species and hybrid proteins. Semin Oncol 24, S9-4–S9-17 (1997)

    Google Scholar 

  28. LaFleur, D.W., Nardelli, B., Tsareva, T., et al.: Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem 276, 39765–39771 (2001)

    Article  CAS  PubMed  Google Scholar 

  29. Conklin, D., Grant, F., Rixon, M., et al: Interferon-epsilon. US Patent 6329175, 2002

    Google Scholar 

  30. Kotenko, S.V., Gallagher, G., Baurin, V.V., et al.: IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4, 69–77 (2003)

    Article  CAS  PubMed  Google Scholar 

  31. Weiss, K.: Safety profile of interferon-alpha therapy. Semin Oncol 25, 9–13 (1998)

    CAS  PubMed  Google Scholar 

  32. Domanski, P., Colamonici, O.R.: The type-I interferon receptor. The long and short of it. Cytokine Growth Factor Rev 7, 143–151 (1996)

    Article  CAS  PubMed  Google Scholar 

  33. Pestka, S.: The human interferon alpha species and receptors. Biopolymers 55, 254–287 (2000)

    Article  CAS  PubMed  Google Scholar 

  34. Schindler, C., Shuai, K., Prezioso, V.R., et al.: Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257, 809–813 (1992)

    Article  CAS  PubMed  Google Scholar 

  35. Fu, X.Y., Schindler, C., Improta, T., et al.: The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A 89, 7840–7843 (1992)

    Article  CAS  PubMed  Google Scholar 

  36. Shuai, K., Schindler, C., Prezioso, V.R., et al.: Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 258, 1808–1812 (1992)

    Article  CAS  PubMed  Google Scholar 

  37. Chen, J., Baig, E., Fish, N.E.: Diversity and relatedness among the type I interferons. J Interferon Cytokine Res 24, 687-9-698 (2004)

    Google Scholar 

  38. Darnell Jr., J.E., Kerr, I.M., Stark, G.R.: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415–1421 (1994)

    Article  CAS  PubMed  Google Scholar 

  39. Ihle, J.N.: The Janus protein tyrosine kinase family and its role in cytokine signaling. Adv Immunol 60, 1–35 (1995)

    Article  CAS  PubMed  Google Scholar 

  40. Parmar, S., Platanias, L.C.: Interferons: mechanisms of action and clinical applications. Curr Opin Oncol 15, 431–439 (2003)

    Article  CAS  PubMed  Google Scholar 

  41. Horvath, C.M., Darnell Jr., J.E.: The antiviral state induced by alpha interferon and gamma interferon requires transcriptionally active Stat1 protein. J Virol 70, 647–650 (1996)

    CAS  PubMed  Google Scholar 

  42. Darnell Jr., J.E.: STATs and gene regulation. Science 277, 1630–1635 (1997)

    Article  CAS  PubMed  Google Scholar 

  43. Aaronson, D.S., Horvath, C.M.: A road map for those who don’t know JAK-STAT. Science 296, 1653–1655 (2002)

    Article  CAS  PubMed  Google Scholar 

  44. Meinke, A., Barahmand-Pour, F., Wohrl, S., et al.: Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons. Mol Cell Biol 16, 6937–6944 (1996)

    CAS  PubMed  Google Scholar 

  45. Farrar, J.D., Smith, J.D., Murphy, T.L., et al.: Recruitment of Stat4 to the human interferon-alpha/beta receptor requires activated Stat2. J Biol Chem 275, 2693–2697 (2000)

    Article  CAS  PubMed  Google Scholar 

  46. Torpey, N., Maher, S.E., Bothwell, A.L., et al.: Interferon alpha but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells. J Biol Chem 279, 26789–26796 (2004)

    Article  CAS  PubMed  Google Scholar 

  47. Matikainen, S., Sareneva, T., Ronni, T., et al.: Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells. Blood 93, 1980–1991 (1999)

    CAS  PubMed  Google Scholar 

  48. Fasler-Kan, E., Pansky, A., Wiederkehr, M., et al.: Interferon-alpha activates signal transducers and activators of transcription 5 and 6 in Daudi cells. Eur J Biochem 254, 514–519 (1998)

    Article  CAS  PubMed  Google Scholar 

  49. Uddin, S., Majchrzak, B., Woodson, J., et al.: Activation of the p38 mitogen-activated protein kinase by type I interferons. J Biol Chem 274, 30127–30131 (1999)

    Article  CAS  PubMed  Google Scholar 

  50. Goh, K.C., Haque, S.J., Williams, B.R.: p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons. EMBO J 18, 5601–5608 (1999)

    Article  CAS  PubMed  Google Scholar 

  51. Li, Y., Sassano, A., Majchrzak, B., et al.: Role of p38a Map kinase in type I interferon signaling. J Biol Chem 279, 970–979 (2004)

    Article  CAS  PubMed  Google Scholar 

  52. Uddin, S., Yenush, L., Sun, X.J., et al.: Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3′-kinase. J Biol Chem 270, 15938–15941 (1995)

    Article  CAS  PubMed  Google Scholar 

  53. Ahmad, S., Alsayed, Y.M., Druker, B.J., et al.: The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J Biol Chem 272, 29991–29994 (1997)

    Article  CAS  PubMed  Google Scholar 

  54. Pestka, S., Krause, C.D., Walter, M.R.: Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202, 8–32 (2004)

    Article  CAS  PubMed  Google Scholar 

  55. Dummer, R., Cozzio, A., Urosevic, M.: Interferons in cutaneous T-cell Lymphomas. Hematol Rep 2(13), 71–74 (2006)

    Google Scholar 

  56. Creasey, A.A., Eppstein, D.A., Marsh, Y.V., et al.: Growth regulation of melanoma cells by interferon and (2′–5′)oligoadenylate synthetase. Mol Cell Biol 3, 780–786 (1983)

    CAS  PubMed  Google Scholar 

  57. Buzaid, A.C., Grimm, E.A., Ali-Osman, F., et al.: Mechanism of the anti-tumor effect of biochemotherapy in melanoma: preliminary results. Melanoma Res 4, 327–330 (1994)

    Article  CAS  PubMed  Google Scholar 

  58. Anderson, C.M., Buzaid, A.C., Sussman, J., et al.: Nitric oxide and neopterin levels and clinical response in stage III melanoma patients receiving concurrent biochemotherapy. Melanoma Res 8, 149–155 (1998)

    Article  CAS  PubMed  Google Scholar 

  59. Bernengo, M.G., Quaglino, P., Cappello, N., et al.: Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients. Melanoma Res 10, 55–65 (2000)

    CAS  PubMed  Google Scholar 

  60. Haller, O., Arnheiter, H., Lindenmann, J., et al.: Host gene influences sensitivity to interferon action selectively for influenza virus. Nature 283, 660–662 (1980)

    Article  CAS  PubMed  Google Scholar 

  61. Sadler, A.J., Williams, B.R.: Interferon-inducible antiviral effectors. Nat Rev Immunol 8, 559–568 (2008)

    Article  CAS  PubMed  Google Scholar 

  62. Aebi, M., Fah, J., Hurt, N., et al.: cDNA structures and regulation of two interferon-induced human Mx proteins. Mol Cell Biol 9, 5062–5072 (1989)

    CAS  PubMed  Google Scholar 

  63. Horisberger, M.A., McMaster, G.K., Zeller, H., et al.: Cloning and sequence analyses of cDNAs for interferon- and virus-induced human Mx proteins reveal that they contain putative guanine nucleotide-binding sites: functional study of the corresponding gene promoter. J Virol 64, 1171–1181 (1990)

    CAS  PubMed  Google Scholar 

  64. Holzinger, D., Jorns, C., Stertz, S., et al.: Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J Virol 81, 7776–7785 (2007)

    Article  CAS  PubMed  Google Scholar 

  65. Gilli, F., Marnetto, F., Caldano, M., et al.: Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1. Mult Scler 12, 47–57 (2006)

    Article  CAS  PubMed  Google Scholar 

  66. Jakschies, D., Hochkeppel, H.K., Horisberger, M.A., et al.: Correlation of the antiproliferative effect and the Mx-homologous protein induction by IFN in patients with malignant melanoma. J Invest Dermatol 95, 238S–241S (1990)

    Article  CAS  PubMed  Google Scholar 

  67. Ralph, S.J., Wines, B.D., Payne, M.J., et al.: Resistance of melanoma cell lines to interferons correlates with reduction of IFN-induced tyrosine phosphorylation. Induction of the anti-viral state by IFN is prevented by tyrosine kinase inhibitors. J Immunol 154, 2248–2256 (1995)

    CAS  PubMed  Google Scholar 

  68. Yurkovetsky, Z.R., Kirkwood, J.M., Edington, H.D., et al.: Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b. Clin Cancer Res 13, 2422–2428 (2007)

    Article  CAS  PubMed  Google Scholar 

  69. Critchley-Thorne, R.J., Yan, N., Nacu, S., et al.: Down-regulation of the interferon signaling pathway in T lymphocytes from patients with metastatic melanoma. PLoS Med 4, e176 (2007)

    Article  PubMed  CAS  Google Scholar 

  70. Takahashi, Y., Kaneda, H., Takasuka, N., et al.: Enhancement of antiproliferative activity of interferons by RNA interference-mediated silencing of SOCS gene expression in tumor cells. Cancer Sci 99, 1650–1655 (2008)

    Article  CAS  PubMed  Google Scholar 

  71. Hanada, T., Yoshimura, A.: Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 13, 413–421 (2002)

    Article  CAS  PubMed  Google Scholar 

  72. Sakai, I., Takeuchi, K., Yamauchi, H., et al.: Constitutive expression of SOCS3 confers resistance to IFN-alpha in chronic myelogenous leukemia cells. Blood 100, 2926–2931 (2002)

    Article  CAS  PubMed  Google Scholar 

  73. Gogas, H., Ioannovich, J., Dafni, U., et al.: Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 354, 709–718 (2006)

    Article  CAS  PubMed  Google Scholar 

  74. Bouwhouis, M., Suciu, S., Kruit, W., et al.: Prognostic value of autoantibodies (auto-AB) in melanoma patients (pts) in the EORTC 18952 trial of adjuvant interferon (IFN) vs Observation (Obs). Proc Am Soc Clin Oncol 25, 8507 (2007). Abstract

    Google Scholar 

  75. Nordlung, J., Kirkwood, J., Milton, B.F.G., et al.: Vitiligo in patients with metastastic melanoma: a good prognostic sign. J. Am. Acad. Dermatol. 9, 689–696; Abstract (1983)

    Google Scholar 

  76. Zeuzem, S., Welsch, C., Herrmann, E.: Pharmacokinetics of peginterferons. Semin Liver Dis 23(suppl 1), 23–28 (2003)

    PubMed  Google Scholar 

  77. Wang, Y.S., Youngster, S., Bausch, J., et al.: Identification of the major positional isomer of pegylated interferon alpha-2b. Biochemistry 39, 10634–10640 (2000)

    Article  CAS  PubMed  Google Scholar 

  78. PEG-Intron: Drug Information, Schering Corporation

    Google Scholar 

  79. Peg-INFa-2a, Pegasus: Drug Information

    Google Scholar 

  80. Balch, C.M., Buzaid, A.C., Soong, S.J., et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19, 3635–3648 (2001)

    CAS  PubMed  Google Scholar 

  81. Dummer, R., Panizzon, R., Bloch, P.H., et al.: Updated Swiss guidelines for the treatment and follow up of cutaneous melanoma. Dermatology 210, 39–44 (2005)

    Article  CAS  PubMed  Google Scholar 

  82. Kirkwood, J.M., Ibrahim, J.G., Sondak, V.K., et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 18, 2444–2458 (2000)

    CAS  PubMed  Google Scholar 

  83. Kirkwood, J.M., Manola, J., Ibrahim, J., et al.: A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res 10, 1670–1677 (2004)

    Article  CAS  PubMed  Google Scholar 

  84. Eggermont, A.M., 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 366, 1189–1196 (2005)

    Article  CAS  PubMed  Google Scholar 

  85. Kirkwood, J.M., Strawderman, M.H., Ernstoff, M.S., et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14, 7–17 (1996)

    CAS  PubMed  Google Scholar 

  86. Eggermont, A.M., 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 372, 117–126 (2008)

    Article  CAS  PubMed  Google Scholar 

  87. Dummer, R., Garbe, C., Thompson, J.A., et al.: Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma. J Clin Oncol 24, 1188–1194 (2006)

    Article  CAS  PubMed  Google Scholar 

  88. Millwald, M.J., Bedikian, A.Y., Conry, R.M., et al.: Randomized multinational phase III trial of dacarbazine( DTIC) with or without Bcl-2 antisense (oblimersen sodium) in patients with advnced maligannt melanoma (MM). Analysis of long-term survival. ASCO Annual Meeting:Abstract No 7505 (2004)

    Google Scholar 

  89. Schadendorf, D., Ugurel, S., Schuler-Thurner, B., et al.: Dacarbazine (DTIC) versus vaccination with autologous 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 17, 563–570 (2006)

    Article  CAS  PubMed  Google Scholar 

  90. Kurokohchi, K., Takaguchi, K., Kita, K., et al.: Successful treatment of advanced hepatocellular carcinoma by combined administration of 5-fluorouracil and pegylated interferon-alpha. World J Gastroenterol 11, 5401–5403 (2005)

    PubMed  Google Scholar 

  91. Son, M.J., Song, H.S., Kim, M.H., et al.: Synergistic effect and condition of pegylated interferon alpha with paclitaxel on glioblastoma. Int J Oncol 28, 1385–1392 (2006)

    CAS  PubMed  Google Scholar 

  92. Hwu, W.J., Panageas, K.S., Menell, J.H., et al.: Phase II study of temozolomide plus pegylated interferon-alpha-2b for metastatic melanoma. Cancer 106, 2445–2451 (2006)

    Article  CAS  PubMed  Google Scholar 

  93. Middleton, M.R., Grob, J.J., Aaronson, N., et al.: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18, 158–166 (2000)

    CAS  PubMed  Google Scholar 

  94. Spieth, K., Kaufmann, R., Dummer, R., et al.: Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG). Ann Oncol 19, 801–806 (2008)

    Article  CAS  PubMed  Google Scholar 

  95. 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 23, 9001–9007 (2005)

    Article  CAS  PubMed  Google Scholar 

  96. Hauschild, A., Dummer, R., Ugurel, S., et al.: Combined treatment with pegylated interferon-alpha-2a and dacarbazine in patients with advanced metastatic melanoma: a phase 2 study. Cancer 113, 1404–1411 (2008)

    Article  CAS  PubMed  Google Scholar 

  97. Vaishampayan, U.N., Heilbrun, L.K., Marsack, C., et al.: Phase II trial of pegylated interferon and thalidomide in malignant metastatic melanoma. Anticancer Drugs 18, 1221–1226 (2007)

    Article  CAS  PubMed  Google Scholar 

  98. Medwatch: What is a serious adverse effect? www.fda.gov. Retrieved on 18 Sep 2007

  99. Hauschild, A., Gogas, H., Tarhini, A., et al.: Practical guidelines for the management of interferon-alpha-2b side effects in patients receiving adjuvant treatment for melanoma: expert opinion. Cancer 112, 982–994 (2008)

    Article  CAS  PubMed  Google Scholar 

  100. Malik, U.R., Makower, D.F., Wadler, S.: Interferon-mediated fatigue. Cancer 92, 1664–1668 (2001)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Merlin Guggenheim .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Guggenheim, M. et al. (2010). Melanoma. In: Dummer, R., Pittelkow, M., Iwatsuki, K., Green, A., Elwan, N. (eds) Skin Cancer - A World-Wide Perspective. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-05072-5_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-05072-5_23

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-05071-8

  • Online ISBN: 978-3-642-05072-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics