A phase 1 study of granulocyte macrophage colony-stimulating factor (sargramostim) and escalating doses of thalidomide in patients with high-risk malignant melanoma.

This phase 1 study evaluated the safety and tolerability of adjuvant treatment with Subcutaneous granulocyte macrophage colony-stimulating factor (GMCSF) administered in combination with escalating doses of thalidomide in patients with surgically resected stage II (T4), III, or IV melanoma at high risk for recurrence. Adjuvant treatment included GM-CSF 125 mu g/m(2) subcutaneously for 14 days and thalidomide at an initial dose of 50 mg/d, escalated in cohorts of 3 to 6 patients each to a maximum of 400mg/d followed by 14 days of rest. Treatment was continued for Lip to 1 year in the absence of disease progression. Of 19 patients treated, the most common toxicities were grade 1/2 constipation (68%), fatigue (58%), neuropathy (42%), bone kind joint pain (37%), and dyspnea, dizziness, injection site skin reaction, and somnolence (32% each). Thrombotic events in 3 of 19 patients (16%), including 1 treatment-related death, were the most serious adverse events kind were thought to be due to thalidomide. With a median follow-up of 945 days (2.6 y), 8 (42%) patients were alive, including I with disease and 7 without evidence of disease. GM-CSF plus thalidomide as adjuvant therapy for patients with resected high-risk melanoma was associated with it high incidence of thrombotic events. Because life-threatening events are unacceptable in the adjuvant setting, up-front antithrombotic prophylaxis will be necessary for further evaluation of GM-CSF plus thalidomide as a viable regimen in this patient group.