title: A phase 1 study of granulocyte macrophage colony-stimulating factor (sargramostim) and escalating doses of thalidomide in patients with high-risk malignant melanoma.
abstract: This phase 1 study evaluated the safety and tolerability of adjuvant treatment with subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF) 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 microg/m2 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 400 mg/d followed by 14 days of rest. Treatment was continued for up 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 and 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 and were thought to be due to thalidomide. With a median follow-up of 945 days (2.6 y), 8 (42%) patients were alive, including 1 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 a 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.
authors.affiliation: Mount Sinai Comprehensive Cancer Center Melanoma Program, Miami Beach, FL 33140, USA. JLutzky@aptiumoncology.com
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.forename: Robert
authors.initials: R
authors.lastname: Weber
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Nunez
authors.forename: Matt
authors.initials: M
authors.lastname: Gillett
authors.forename: Lynn
authors.initials: L
authors.lastname: Spitler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D013792:Thalidomide; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor