Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor

Purpose: To evaluate granulocyte-macrophage colany-stimulating factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk of recurrence. Patients and Methods: Forty-eight assessable patients with stage III or IV melanoma were treated in a phase II trial with long-term, chronic, intermittent GM-CSF after surgical resection of disease. Patients with stage III disease were required to have more than four positive nodes or a more than 3-cm mass, All patients were rendered clinically disease-free by surgery before enrollment. The GM-CSF wets administered subcutaneously in 28-day cycles, such that a dose of 125 mu g/m(2) was delivered daily for 14 days followed by 14 days of rest. Treatment cycles continued for 1 year or until disease recurrence. Patients were evaluated for toxicity and disease-free and overall survival. Results: Overall and disease-free survival were significantly prolonged in patients who received GM-CSF compared with matched historical controls. The median survival duration was 57.5 months in the study patients versus 12.2 months in the matched controls (P < .001). GM-CSF wets well tolerated; only one subject discontinued drug due to an adverse event (grade 2 injection site reaction). Conclusion: GM-CSF may provide an antitumor effect that prolongs survival and disease-free survival in patients with stage III and IV melanoma who are clinically disease-free. These results support institution of a prospective, randomized clinical trial to definitively determine the value of surgical adjuvant therapy with GM-CSF in such patients, J Clin Oncol 18:1614-1621. (C) 2000 by American Society of Clinical Oncology.