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Adjuvant Therapy of Stage III and IV Malignant Melanoma Using Granulocyte-Macrophage Colony-Stimulating Factor

From the Northern California Melanoma CenterSan Francisco, CA; Massachusetts General Hospital, Boston, MA; Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH; Immunex R & D Corp, Seattle, WA; and University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL.

Address reprint requests to Lynn E. Spitler, MD, Northern California Medical Center, St Francis Memorial Hospital, 900 Hyde St, San Francisco, CA 94109; email lynn{at}drspitler.com

PURPOSE: To evaluate granulocyte-macrophage colony-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 was administered subcutaneously in 28-day cycles, such that a dose of 125 µg/m² 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 37.5 months in the study patients versus 12.2 months in the matched controls (P < .001). GM-CSF was 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.

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