Sequential Administration of GM-CSF (Sargramostim ® ) and IL-2 ± Autologous Vaccine as Adjuvant Therapy in Cutaneous Melanoma: An Interim Report of a Phase II Clinical Trial

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are 2 cytokines with distinct mechanisms of action that complement one another in the adjuvant management of melanoma. Forty-five patients with high-risk melanoma were enrolled in an open-label, single-arm, phase II clinical trial to examine the safety, tolerability, and effectiveness of this combination. After potentially curative surgery, each patient received 12 months of GM-CSF 125 μg/m²/d subcutaneously (SC) for 14 days followed by IL-2, 9 million IU/m²/d SC for 4 days (given every other cycle from months 7–12), followed by 10 days of no treatment. In addition, patients who had tumors yielding an adequate number of live cells received autologous melanoma vaccines. For months 13–24, patients received only GM-CSF 250 μg/m² twice weekly. This is an interim analysis based on the 45 enrolled patients with a median of 15.9 months follow-up (range, 1–50 months). Thirty-two patients are alive: 9 of 13 with stage IV resected melanoma, 16 of 25 with stage III disease, and 7 of 7 with stage II disease. Twelve died of the disease, and one due to stroke. Adjuvant use of sequential GM-CSF and IL-2 ± autologous vaccine was well tolerated with good patient compliance and seemed to benefit high-risk patients with surgically resected melanoma.