title: A phase II study of gefitinib in patients with metastatic melanoma.
abstract: Gefitinib is an inhibitor of the epidermal growth factor receptor, which is frequently expressed on both choroidal and nonchoroidal melanoma cells. We evaluated the clinical efficacy of gefitinib in patients with metastatic melanoma. Patients with stage IV or unresectable stage III melanoma and Zubrod performance status of less than or equal to 2 were eligible. Previous systemic treatment for metastatic disease was required. The dose of oral gefitinib was 250 mg administered daily, and tumor response was evaluated every 6 weeks. Forty-six patients with nonchoroidal melanoma and six with choroidal melanoma were treated, and 48 were evaluable for response. The median age was 62.5 years. Forty-one patients (79%) had stage M1c disease. There were no drug-related grade 4 or 5 adverse events, and fatigue was the only grade 3 adverse event that occurred in more than 5% of patients. Two patients (4%) had partial responses and 13 patients (27%) had disease stabilization. The two responders had a median duration of response of 10.9 months. The median overall progression-free survival was 1.4 months and the median overall survival was 9.7 months. Among the patients with sufficient tissues obtained before and 6 weeks after starting gefitinib administration, there were no notable trends in the changes of the tumoral expression of p-ERK1/2, p-AKT, PAK1, and serum levels of vascular endothelial growth factor or IL-8 with treatment. We concluded that gefitinib was well tolerated but had minimal clinical efficacy as a single-agent therapy for unselected patients with metastatic melanoma.
authors: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Sapna P
authors: SP
authors: Patel
authors: Kevin B
authors: KB
authors: Kim
authors: Nicholas E
authors: NE
authors: Papadopoulos
authors: Wen-Jen
authors: WJ
authors: Hwu
authors: Patrick
authors: P
authors: Hwu
authors: Victor G
authors: VG
authors: Prieto
authors: Menashe
authors: M
authors: Bar-Eli
authors: Maya
authors: M
authors: Zigler
authors: Andrey
authors: A
authors: Dobroff
authors: Yulia
authors: Y
authors: Bronstein
authors: Roland L
authors: RL
authors: Bassett
authors: Anna G
authors: AG
authors: Vardeleon
authors: Agop Y
authors: AY
authors: Bedikian
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002830:Choroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib