10/30/06 Melanoma 101 based on the Interlukin-2 Therapy

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“MELANOMA POSES AN increasingly important health problem.

It is estimated that by the end of 1999, the lifetime risk of developing melanoma in the United States will have reached one in 75.1 Although surgery with or without interferon alfa (IFN ) therapy can be curative in stage I, II, or III disease, a large number of patients will develop distant metastases.

Disseminated metastatic disease is associated with a poor prognosis and a mortality rate of more than 95%. In several large series, survival correlated inversely with the number of involved organ sites, visceral involvement, the disease-free interval, and performance status (PS).2-4 Several treatment options are available to patients with metastatic disease, including single-agent dacarbazine (DTIC) chemotherapy, a variety of combination chemotherapy regimens, and combinations of chemotherapy with tamoxifen or IFN . DTIC chemotherapy produces responses in approximately 20% of patients, with a median response duration of 4 to 6 months, a 5-year survival rate of 2%, and a median survival time of 6 to 9 months.5 Although single-institution phase II studies and small phase III trials have shown that combination chemotherapy, or the addition of either tamoxifen or IFN to DTIC chemotherapy, has potential benefit, no regimen has yet proved superior to DTIC chemotherapy alone.6-13


Interleukin 2 (IL-2), a T-cell growth factor, was first identified in 1976,14 and isolation of the cDNA clone was described in 1983.15

Subsequently, recombinant IL-2 (rIL-2) was shown to have potent antitumor activity in a number of murine tumor models.16 Based on animal model data, a high-dose IL-2 regimen was developed in which IL-2 was administered by short intravenous infusion every 8 hours, with or without lymphokine-activated killer cells.17,18 High-dose bolus IL-2, as a single agent, received United States Food and Drug Administration approval in 1992 after demonstration of durable responses in patients with metastatic renal cell carcinoma.19 In this report, we describe findings from a recently updated 270-patient database of metastatic melanoma patients treated with the same high-dose IL-2 regimen between 1985 and 1993.”