GM-CSF and IL-2 combination as adjuvant therapy in cutaneous melanoma: early results of a phase II clinical trial.

Cytokines have been used in the treatment of patients with cutaneous melanoma. Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) leads to dendritic cell/macrophage priming and activation, and also increases interleukin-2 (IL-2) receptor expression on T. lymphocytes. IL-2 creates lymphokine-activated killer cells and tumor-infiltrating lymphocyte cells. In this open-label, single-arm study of 16 high-risk patients, we combined these two agents to take advantage of their different but complementary functions. All patients underwent potentially curative surgery. Postoperatively, each patient received GM-CSF at 125 microg/m2/d subcutaneously (SC) for 14 days; this was followed by IL-2 at 9 million IU/m2/d SC for 4 days, and then 10 to 12 days of no treatment. In addition, patients who had large tumors that could yield over 100 million live tumor cells received autologous melanoma vaccines. The duration of follow-up ranged from 21 to 42 months (median: 27 months). During follow-up, five patients developed metastases. This program was carried out on an outpatient basis, and no hospitalization was required. It was well tolerated with minimal side effects. The combination treatment regimen of GM-CSF and IL-2 with or without autologous vaccine used adjuvantly appears to benefit high-risk melanoma patients; further clinical testing of this regimen is warranted.