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Opinion statement

The overall survival for patients with metastatic melanoma ranges from 4.7 to 11 months, with a median survival of 8.5 months. Standard treatment for patients with metastatic melanoma has not been defined. The range of treatment options includes close observation, surgical resection of isolated metastases, therapy with dacarbazine, combination chemotherapy, and participation in clinical trials.

Numerous chemotherapeutic agents have shown activity in the treatment of malignant melanoma. Dacarbazine (DTIC-Dome; Bayer Corporation, West Haven, CT) has a response rate of 15% to 20% and remains the reference agent for the treatment of metastatic disease. Additional agents with single-agent activity include cisplatin, (Platinol-AQ; Bristol-Myers Oncology, Princeton, NJ); carmustine (BiCNU; Bristol-Myers Oncology, Princeton, NJ); paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ); and docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Collegeville, PA). Temozolomide (Temodar; Schering-Plough, Kenilworth, NJ), which is essentially an oral form of dacarbazine but with greater central nervous system penetrance, is associated with a response rate of 20%.

Combination chemotherapy with or without tamoxifen has been extensively evaluated in patients with metastatic melanoma. Although the initial results with the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) were associated with overall response rates of 50% to 55% in single-institution studies, results from larger multicenter studies reveal responses rates ranging from 10% to 20%. Based on the results of several clinical trials, there is no evidence that the addition of tamoxifen improves the response rate. Another combination regimen is cisplatin, vinblastine, and dacarbazine (CVD), which is associated with a 20% to 25% response rate.

There has been widespread interest in developing immunotherapies against metastatic melanoma. Interferon (IFN)-alfa and interleukin (IL)-2 as single agents have produced response rates in the 15% to 20% range.

Biochemotherapy, which is a combination of immunotherapy and cytotoxic chemotherapy, has been studied in patients with metastatic melanoma. Multiple phase II studies have demonstrated high response rates but unclear impact on overall survival. Therapy is associated with significant toxicity. Ongoing randomized clinical trials will clarify the role of biochemotherapy in patients with metastatic melanoma.

Ongoing new approaches to treatment include the therapeutic use of vaccines alone or in combination with cytokines.

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References and Recommended Reading

  1. Balch CM, Soong S-J, Shaw HM, et al.: An analysis of prognostic factors in 8500 patients with cutaneous melanoma. In Cutaneous Melanoma edn 2. Edited by Balch CM, Houghton AN, Milton GW, et al. Philadelphia: JB Lippincott, 1992:165.

    Google Scholar 

  2. Barth A, Wanek LA, Morton D: Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 1995, 181:193.

    PubMed  CAS  Google Scholar 

  3. Ahmann DL, Creagan ET, Hahn RG, et al.: Complete responses and long-term survivals after systemic chemotherapy for patients with advanced malignant melanoma. Cancer 1989, 63:224–227.

    Article  PubMed  CAS  Google Scholar 

  4. Lee SM, Betticher DC, Thatcher N: Melanoma: chemotherapy. Br Med Bull 1995, 51:609–630.

    PubMed  CAS  Google Scholar 

  5. Hill G II, Krementz E, Hill H: Dimethyl triazenol imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy. Central Oncology Grow Protocols 7130, 7131, and 7131A. Cancer 1984, 53:1299.

    Article  PubMed  Google Scholar 

  6. Legha SS, Ring S, Papadopoulsa N, et al.: A phase II trial of taxol in metastatic melanoma. Cancer 1990, 65:2478–2481.

    Article  PubMed  CAS  Google Scholar 

  7. Einzig AI, Hochster H, Wiernik PH, et al.: A phase II study of taxol in patients with malignant melanoma. Invest New Drugs 1991, 9:59–64.

    Article  PubMed  CAS  Google Scholar 

  8. 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, 13:111–117.

    Article  PubMed  CAS  Google Scholar 

  9. Bleehen NM, Newlands SM, Thatcher LN, et al.: Cancer research campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 1995, 13:910–913.

    PubMed  CAS  Google Scholar 

  10. Summers Y, Middleton MR, Calvert H, et al.: Effect of Temozolomide (TMZ) on central nervous system (CNS) relapse in patients with advanced melanoma. Proc Am Soc Clin Oncol 1999, 18:A2048.

    Google Scholar 

  11. 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, 68:1403–1405. This is the first paper reporting the activity of the Dartmouth regimen.

    Google Scholar 

  12. Legha SS, Ring S, Papadopoulos N, et al.: A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. Cancer 1989, 64:2024.

    Article  PubMed  CAS  Google Scholar 

  13. McClay EF, Mastrangelo MJ, Berd D, et al.: Effective combination chemo/hormonal therapy for malignant melanoma: experience with three consecutive trials. Int J Cancer 1992, 50:553–556.

    Article  PubMed  CAS  Google Scholar 

  14. Margolin KA, Liu P-Y, Flaherty LE, et al.: Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a southwest oncology group study. J Clin Oncol 1998, 16:664–669. Results of the large phase II study of the Dartmouth regimen.

    PubMed  CAS  Google Scholar 

  15. Saxman SB, Meyers ML, Chapman PB, et al.: A phase III multicenter randomized trial of DTIC, cisplatin, BCNU and tamoxifen versus DTIC alone in patients with metastatic melanoma. J Clin Oncol 1999, 18:A2068. Very important paper that showed lack of benefit of the Dartmouth regimen in a randomized clinical study.

    Google Scholar 

  16. Buzaid AC, Legha S, Winn R, et al.: Cisplatin (C) vinblastine (V), and dacarbazine (D) (CVD) versus dacarbazine alone in metastatic melanoma: preliminary results of a phase III Cancer Community Oncology program (CCOP) trial [abstract]. Proc Am Soc Clin Oncol 1993, 12:389.

    Google Scholar 

  17. Argawala SS, Kirkwood JM: Interferons in melanoma. Curr Opin Oncol 1996, 8:167.

    Google Scholar 

  18. Atkins MB: The treatment of metastatic melanoma with chemotherapy and biologics. Curr Opin Oncol 1997, 9:205.

    PubMed  CAS  Google Scholar 

  19. Kirkwood JM, Strwderman 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.

    PubMed  CAS  Google Scholar 

  20. Atkins MB, Lotze M, Dutcher JP, et al.: High dose recombinant interleukin-2 therapy for patients with metastatic melanoma: analysis of 270 patients treated from 1985–1993. J Clin Oncol 1999, 17:2105–2116. Updated analysis of IL-2 data that led to FDA approval for IL-2 in advanced melanoma.

    PubMed  CAS  Google Scholar 

  21. 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 alfa-2a in patients with advanced melanoma. J Clin Oncol 1993, 11:1969.

    PubMed  CAS  Google Scholar 

  22. Falkson CI, Ibrahim J, Kirkwood JM, et al.: Phase III trial of dacarbazine versus dacarbazine with interferon a-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon a-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 1998, 16:1743–1751.

    PubMed  CAS  Google Scholar 

  23. Legha SS, Ring S, Eton O, et al.: Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol 1998, 16:1752–1759.

    PubMed  CAS  Google Scholar 

  24. Stoter G, Aamdal S, Rodenhuis S, et al.: Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. J Clin Oncol 1991, 9:1687–1691.

    PubMed  CAS  Google Scholar 

  25. Richards JM, Mehta N, Ramming K, et al.: Sequential chemotherapy/immunotherapy in the treatment of metastatic melanoma. J Clin Oncol 1992, 10:1388–1343.

    Google Scholar 

  26. Atkins MS, O’Boyle KR, Sosman JA, et al.: Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. J Clin Oncol 1994, 12:1553.

    PubMed  CAS  Google Scholar 

  27. Rosenberg SA, Yang JC, Schwartzentruber DJ, et al.:Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 1999, 17:968–975. One of the first randomized trials of biochemotherapy.

    PubMed  CAS  Google Scholar 

  28. Ang K, Geara F, Byers R, Peters L: Radiotherapy for melanoma. In Cutaneous Melanoma edn 3. Edited by Balch CM. St. Louis: Quality Medical Publishing; 1998:389–403.

    Google Scholar 

  29. Karakousis CP, Velez A, Driscoll DL, et al.: Metastectomy in malignant melanoma. Surgery 1994, 115:295.

    PubMed  CAS  Google Scholar 

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Sun, W., Schuchter, L.M. Metastatic melanoma. Curr. Treat. Options in Oncol. 2, 193–202 (2001). https://doi.org/10.1007/s11864-001-0033-5

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  • DOI: https://doi.org/10.1007/s11864-001-0033-5

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