Summary
The incidence of malignant melanoma has increased at an alarming rate over the past few decades. Indications are that it will continue to rise in the foreseeable future. Primary prevention of malignant melanoma through education of the general public regarding the hazards of sun exposure is important in an attempt to reduce the incidence of the disease in the future. It can, however, be expected to take many years before a decrease in the number of cases of this disease is seen. Until such time, the medical oncologist will be faced with an increasing number of referrals for both adjuvant therapy and treatment of metastatic disease.
Many agents have been investigated as possible postsurgical adjuvant therapies in patients with malignant melanoma. To date, interferon-α (IFN-α) given initially intravenously in high doses followed by subcutaneous therapy for 1 year, is the only treatment that has been shown to increase disease-free and overall survival in patients with high-risk melanomas. Patients falling into this group should still, wherever possible, be enrolled in prospectively randomised clinical trials.
Although the prognosis for patients with metastatic melanoma remains poor, some progress in the management of this disease has been made. It has not yet been conclusively proven that combination chemotherapy yields superior results to single agent dacarbazine (DTIC) [which has for many years formed the cornerstone of therapy].
Immunotherapy involving IFNs and interleukin-2 (IL-2) alone or in combination has yielded similar results to those achieved with chemotherapy alone. The combination of chemotherapy plus immunotherapy appears to hold promise, with high response rates and often durable remissions reported, albeit at the expense of considerable treatment-related toxicity. Novel therapies including tumour vaccines and gene therapy also hold promise for the future management of this disease.
Similar content being viewed by others
References
Barth A, Morton DL. The role of adjuvant therapy in melanoma management. Cancer 1995; 75; 726–34
Veronesi U, Adamus J, Aubert C, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med 1982; 307: 913–6
Lejune FJ, Macher E, Kleeberg U, et al. An assessment of DTIC versus levamisole or placebo in the treatment of high risk stage I patients after surgical removal of a primary melanoma of the skin: a phase III adjuvant study (EORTC protocol 18761). Eur J Cancer 1988; 24 Suppl. 2: 81–90
Hill II GJ, Moss SE, Golomb FM, et al. DTIC and combination therapy for melanoma, III: DTIC (NSC 45388) Surgical Adjuvant Study COG protocol 7040. Cancer 1981; 47: 2556–62
Retsas S, Quigley M, Pectasides D, et al. Clinical and histologic involvement of regional lymph nodes in malignant melanoma: adjuvant vindesine improves survival. Cancer 1994; 73: 2119–30
Retsas S, Mohith A, MacRae K, et al. First interim analysis of adjuvant vindesine (V) and DTIC (D) (AVD) for clinical and histologie involvement of regional lymph nodes in malignant melanoma (CHRLNM) [abstract no. 112]. 2nd International Conference on Adjuvant Therapy of Malignant Melanoma; 1997 Mar 14–15; London
Pectasides D, Alevizakos N, Bafaloukos D, et al. Adjuvant chemotherapy with dacarbazine, vindesine, and cisplatin in pathological stage II malignant melanoma. Am J Clin Oncol 1994; 17: 55–9
Quirt IC, Shelley WE, Pater JL, et al. Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1991; 9: 729–35
Loutfi A, Shakr A, Jerry M, et al. Double blind randomized prospective trial of levamisole/placebo in stage I cutaneous malignant melanoma. Clin Invest Med 1987; 10: 325–8
Spitler LE. A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma. J Clin Oncol 1991; 9: 736–40
Fisher RI, Terry WD, Hodes RJ, et al. Adjuvant immunotherapy or chemotherapy for malignant melanoma: preliminary report of the National Cancer Institute randomized clinical trial. Surg Clin North Am 1981; 61: 1267–77
Morton DL, Eilber FR, Malmgren RA, et al. Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 1970; 68: 158–64
Sterchi JM, Wells HB, Case LD, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in Stage I and Stage II cutaneous melanoma: an interim report. Cancer 1985; 55: 707–12
Morton DL. Adjuvant immunotherapy of malignant melanoma: status of clinical trials at UCLA. Int J Immunotherapy 1986; II: 31–6
Wood WC, Cosimi AB, Carey RW, et al. Randomized trial of adjuvant therapy for ‘high risk’ primary malignant melanoma. Surgery 1978; 83: 677–81
Pinsky CM, Hirshaut Y, Wanebo HJ, et al. Surgical adjuvant immunotherapy with BCG in patients with malignant melanoma: results of a prospective, randomized trial. In: Terry WD, Windhorst D, editors. Immunotherapy of cancer: present status of trials in man. New York: Raven, 1978: 27–33
Ariyan S, Kirkwood JM, Mitchell MS, et al. Intralymphatic and regional surgical adjuvant immunotherapy in high-risk melanoma of the extremities. Surgery 1982; 92: 459–63
Cascinelli N, Rumke P, MacKie R, et al. The significance of conversion of skin reactivity to efficacy of bacillus Calmette-Guérin (BCG) vaccinations given immediately after radical surgery in stage II melanoma patients. Cancer Immunol Immunother 1989; 28: 282–6
Spitler LE, Grossbard ML, Ernstoff MS, et al. Adjuvant therapy of stage III and IV malignant melanoma using yeast derived GM-CSF [abstract no. 115]. 2nd International Conference on Adjuvant Therapy of Malignant Melanoma, 997 Mar 14–15, London
Lipton A, Harvey HA, Lawrence B, et al. Corynebacterium parvum versus BCG adjuvant immunotherapy in human malignant melanoma. Cancer 1983; 51: 57–60
Balch CM, Murray DR, Presant C, et al. Southeastern Cancer Study Group: a randomized prospective comparison of BCG versus C. parvum adjuvant immunotherapy in melanoma patients with resected metastatic lymph nodes [abstract]. Proc Am Soc Clin Oncol 1984; 3: 236
Thatcher N, Mene A, Banerjee SS, et al. Randomized study of Corynebacterium parvum adjuvant therapy following surgery for (stage II) malignant melanoma. Br J Surg 1986; 73: 111–5
Creagan ET, Dalton RJ, Ahmann DL, et al. Randomized surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol 1995; 13: 2776–83
Cascinelli N, Bufalino R, Morabito A, et al. Results of adjuvant interferon study in WHO melanoma programme [letter]. Lancet 1994; 343: 913–4
Meyskens Jr FL, Kopecky KJ, Taylor CW, et al. Randomized trial of adjuvant human interferon gamma versus observation in high-risk cutaneous melanoma: a Southwest Oncology Group study. J Natl Cancer Inst 1995; 87: 1710–3
Kirkwood JM, Strawderman MH, Ernstoff MS, et al. Interferon Alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996; 14: 7–17
Carubia JM, Yu RK, Macala LJ, et al. Gangliosides of normal and neoplastic human melanocytes. Biochem Biophys Res Comm 1984; 120: 500–4
Morton DL, Foshag LJ, Hoon DS, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 1992; 216: 463–82
Berd D, Maguire Jr HC, McCue P, et al. Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunological results in 64 patients. J Clin Oncol 1990; 8: 1858–67
Mitchell MS, Harel W, Kan-Mitchell J, et al. Active specific immunotherapy of melanoma with allogeneic cell lysates: rationale, results, and possible mechanisms of action. Ann NY Acad Sci 1993; 690: 153–66
Livingston PO, Natoli EJ, Calves MJ, et al. Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients. Proc Natl Acad Sci USA 1987; 84: 2911–5
Livingston PO, Wong GYC, Adluri S, et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 1994; 12: 1036–44
Balch CM, Houston A, Peter L. Cutaneous melanoma. In: De Vita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practices of oncology. 3rd ed. Philadelphia: Lippincott, 1989: 1499–542
Ho RCS. Medical management of stage IV malignant melanoma: medical issues. Cancer 1995; 75: 735–41
Comis RL. DTIC (NSC-45388) in malignant melanoma: a perspective. Cancer Treat Rep 1976; 60; 165–76
Hill II GJ, Krementz ET, Hill HZ. Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma: IV Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A). Cancer 1984; 53: 1299–305
Bleehen NM, Newlands ES, Lee SM, et al. Cancer Research Campaign phase II trial of temozolamide in metastatic melanoma. J Clin Oncol 1995; 13: 910–3
Costanza ME, Nathanson L, Schoenfeld D, et al. Results with methyl-CCNU and DTIC in metastatic melanoma. Cancer 1977; 40: 1010–5
Cohen MH, Schoenfeld D, Wolter J. Randomized trial of chlorpromazine, caffeine and methyl-CCNU in disseminated melanoma. Cancer Treat Rep 1980; 64: 151–3
Khayat D, Giroux B, Berille J, et al. Fotemustine in the treatment of brain primary tumors and metastases. Cancer Invest 1994; 12: 414–20
Falkson CI, Falkson G, Falkson HC. Phase II trial of fotemustine in patients with metastatic malignant melanoma. Invest New Drugs 1994; 12: 251–4
Avril MF, Bonneterre J, Cupissol D, et al. Fotemustine plus dacarbazine for malignant melanoma. Eur J Cancer 1992; 28A: 1807–11
Binder M, Winkler A, Dorffner R, et al. Fotemustine plus dacarbazine in advanced stage III malignant melanoma. Eur J Cancer 1992; 28A: 1814–6
Oliver V, Aliaga A, Lopez Lopez JJ, et al. Long-term complete remissions in patients with disseminated melanoma treated by fotemustine and dacarbazine [letter]. Eur J Cancer 1993; 29A: 287
Merimsky O, Inbar M, Chaitchik S. Fotemustine and DTIC combination in patients with disseminated malignant melanoma. Am J Clin Oncol 1992; 15: 84–6
Lee SM, Margison GP, Woodcock AA, et al. Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. Br J Cancer 1993; 67: 1356–60
Aamdal S, Gerard B, Bohman T, et al. Sequential administration of dacarbazine and fotemustine in patients with disseminated malignant melanoma — an effective combination with unexpected toxicity. Eur J Cancer 1992; 28: 447–50
Balch CM, Houghton AN, Peters LJ. Cutaneous melanoma. In: de Vita Jr VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. Philadelphia: Lippincott Co, 1993: 1612–61
Legha SS, Ring S, Bedikian A, et al. Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha. Ann Oncol 1996; 7: 827–35
Glover D, Glick J, Weiler C, et al. High dose cis-platinum (DDP) and WR-2721 in metastatic melanoma. Proc Am Soc Clin Oncol 7: 247, 1988
Luger SM, Kirkwood JM, Ernstoff MS, et al. High-dose cisplatin and dacarbazine in the treatment of metastatic melanoma. J Natl Cancer Inst 1990; 82: 1934–7
Chang A, Hunt M, Parkingson DR, et al. Phase II trial of carboplatin in patients with metastatic malignant melanoma: a report from the Eastern Cooperative Oncology Group. Am J Clin Oncol 1993; 16: 152–5
Olver I, Green M, Peters W, et al. A phase II trial of zeniplatin in metastatic melanoma. Am J Clin Oncol 1995; 18: 56–8
Kirkwood JM. Preclinical studies, experimental therapeutics, and clinical management of advanced melanoma [review]. Curr Opin Oncol 1992; 4: 368–79
Einzig AI, Schuchter LM, Recio A, et al. Phase II trial of docetaxel (taxotere) in patients with metastatic melanoma previously untreated with cytotoxic chemotherapy. Med Oncol 1996; 13: 111–7
Bedikian AY, Weiss GR, Legha SS, et al. Phase II trial of docetaxel in patients with advanced cutaneous malignant melanoma previously untreated with chemotherapy. J Clin Oncol 1995; 13: 2895–9
Sessa C, Aamdal S, Wolff I, et al. Gemcitabine in patients with advanced malignant melanoma or gastric cancer: phase II studies of the EORTC Early Clinical Trials Group. Ann Oncol 1994; 5: 471–2
Sondak VK, Kopecky KJ, Liu PY, et al. Didemnin B in metastatic malignant melanoma: a phase II trial of the Southwest Oncology Group. Anti-Cancer Drugs 1994; 5: 147–50
Del Prete SA, Maurer LH, O’Donnell J, et al. Combination chemotherapy with cisplatin, carmustine, dacarbazine and tamoxifen in metastatic melanoma. Cancer Treat Rep 1984; 68: 1403–5
McClay EF, Mastrangelo MJ, Bellet RE, et al. Combination chemotherapy and hormonal therapy in the treatment of malignant melanoma. Cancer Treat Rep 1987; 71: 465–9
McClay EF, Mastrangelo MJ, Bellett RE, et al. An effective chemo/hormonal therapy regimen for the treatment of disseminated malignant melanoma. Proc Am Soc Clin Oncol 1989; 8: 282
Mastrangelo MJ, Bellett RE, Berd D. Aggressive chemotherapy for melanoma. In: de Vita Jr VT, Hellman S, Rosenberg SA, editors. Principles and practice of oncology update. Vol. 5. Philadelphia: Lippincott, 1991: 1–11
McClay EF, McClay ME. Tamoxifen: is it useful in the treatment of patients with metastatic melanoma? [review]. J Clin Oncol 1994; 12: 617–26
Rusthoven JJ, Quirt IC, Iscoe NA, et al. Randomized, double-blind placebo-controlled trial comparing the response rates of carmustine, dacarbazine and cisplatin with or without tamoxifen in patients with metastatic melanoma. J Clin Oncol 1996; 14: 2083–90
Falkson CI, Ibrahim J, Kirkwood J, et al. A randomized phase III trial of dacarbazine (DTIC) versus DTIC + interferon alfa-2b (IFN) versus DTIC + tamoxifen (TMX) versus DTIC + IFN + TMX in metastatic malignant melanoma: an ECOG trial [abstract no. 1350]. Proc Am Soc Clin Oncol 1996; 15: 435
Lazarus HM, Herzig RH, Wolff SN, et al. Treatment of metastatic malignant melanoma with intensive melphalan and autologous bone marrow transplantation. Cancer Treat Rep 1985: 69; 473–7
McElwain TJ, Hedley DW, Burton G, et al. Marrow auto transplantation accelerates hematological recovery in patients with malignant melanoma treated with high-dose melphalan. Br J Cancer 1979: 40; 72–80
Meisenberg B. High-dose chemotherapy and autologous stem cell support for patients with malignant melanoma [review]. Bone Marrow Transplant 1996; 17: 903–6
Agarwala SS, Kirkwood JM. Interferons in the therapy of solid tumors. Oncology 1994; 51: 129–36
Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985: 313; 1485–92
Sparano JA, Fisher RI, Sunderland M, et al. Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alpha-2a in patients with advanced melanoma. J Clin Oncol 1993; 11: 1969–77
Keilholz U, Scheibenbogen C, Tilgen W, et al. Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma: comparison of two phase II trials. Cancer 1993; 72: 607–14
Falkson CI, Falkson G, Falkson HC. Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol 1991: 9; 1403–8
Kirkwood JM, Ernstoff MS, Giuliano A, et al. Interferon alpha-2a and dacarbazine in melanoma. J Natl Cancer Inst 1990: 82; 1062–3
Thompson DB, Adena M, McLeod GR, et al. Interferon-α2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. Melanoma Res 1993: 3; 133–8
Bajetta E, Di Leo A, Zampino MG, et al. 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 1994; 12: 806–11
Nabel GJ, Nabel EG, Yang ZY, et al. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity and lack of toxicity in humans. Proc Natl Acad Sci USA, 1993:90; 11307–11
Rosenberg SA. Gene therapy for cancer. JAMA 1992: 268; 2416–9
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cohen, G.L., Falkson, C.I. Current Treatment Options for Malignant Melanoma. Drugs 55, 791–799 (1998). https://doi.org/10.2165/00003495-199855060-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199855060-00006