Phase IB study to evaluate efficacy and tolerability of olaparib (AZD2281) plus gefitinib in patients (P) with epidermal growth factor receptor (EGFR) mutation positive advanced non-small cell lung cancer (NSCLC) (NCT=1513174/GECP-GOAL)
| Autor: | Margarita Majem, Juan Luis Marti-Ciriquian, Miguel Angel Molina-Vila, Rosario Garcia Campelo, Pablo Martinez, Enriqueta Felip, Felipe Cardenal, Cinta Pallares, Guillermo Alonso-Jaudenes Curbera, Clara Mayo de las Casas, Maria Carmen Gonzalez-Arenas, Ramon Palmero, Rafael Rosell, Enric Carcereny Costa, Bartomeu Massuti, Maria Sanchez-Ronco |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty biology business.industry non-small cell lung cancer (NSCLC) Pharmacology medicine.disease Oncogene Addiction respiratory tract diseases Olaparib chemistry.chemical_compound Gefitinib Tolerability chemistry Pharmacokinetics Internal medicine medicine biology.protein Erlotinib Epidermal growth factor receptor business neoplasms medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 32:8079-8079 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 8079 Background: Progression-free survival (PFS) and response rate (RR) to EGFR tyrosine kinase inhibitors (TKIs) vary in P with NSCLC driven by EGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. High BRCA1 mRNA expression negatively influenced PFS among EGFR mutant P treated with erlotinib. We hypothesized that since olaparib can attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve PFS in these P. Methods: This is a Phase IB dose escalation study (standard 3+3 design) to identify the maximum tolerated dose (MTD), dose limiting toxicity (DLT), pharmacokinetics (PK), and clinical activity of orally administered olaparib in combination with gefitinib in EGFR mutant advanced NSCLC. P were treated with gefitinib 250mg once daily plus olaparib at escalating doses ranging from 100mg BID to 250mg TDS during a 28-day cycle. Results: Twenty-two P were included across four dose levels of olaparib: 100mg BID (3), 200mg BID (6), 200mg ... |
| Databáze: | OpenAIRE |
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