AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: An open-label, randomized, multicenter, phase II study
| Autor: | J. A. Sosman, Clive Morris, Mireille Cantarini, C. Robert, John M. Kirkwood, R. Dummer, Lars Bastholt, Mark R. Middleton, K Kemsley, Paul B. Chapman |
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| Rok vydání: | 2008 |
| Předmět: |
Oncology
Neuroblastoma RAS viral oncogene homolog Cancer Research medicine.medical_specialty Chemotherapy education.field_of_study Pathology Temozolomide business.industry Melanoma medicine.medical_treatment Population Phases of clinical research medicine.disease Primary tumor Internal medicine medicine business education medicine.drug Advanced melanoma |
| Zdroj: | JOURNAL OF CLINICAL ONCOLOGY. 26(15) |
| ISSN: | 0732-183X |
| Popis: | 9033 Background: AZD6244 is an orally available, potent, selective, ATP uncompetitive inhibitor of MEK1/2, with preclinical and phase I data suggesting it has the potential for anti-tumor activity in pts with melanoma. Here we evaluate the efficacy and safety of AZD6244 vs TMZ in an overall population of advanced melanoma pts and in mutated BRAF (BRAF+) or mutated NRAS (NRAS+) subgroups. Methods: Eligibility included AJCC stage 3/4 malignant melanoma, RECIST measurable disease, and no prior chemotherapy for advanced melanoma. Pts were randomized 1:1 to AZD6244 (100mg BD continuously) or TMZ (200 mg/m2 for 5 days, q28d). Pts randomized to TMZ could receive AZD6244 after disease progression. The primary outcome variable was progression-free survival (PFS), which was then adjusted for source of primary tumor (uveal vs non-uveal), mutation status, LDH (> or ≤2 x ULN), and WHO PS (0–2). Mutation status was assessed in archival or fresh tumor samples by DNA sequencing. Results: A total of 104 and 96 pts were ra... |
| Databáze: | OpenAIRE |
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