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Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers.
- Source :
-
Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2017 Oct; Vol. 112, pp. 195-199. Date of Electronic Publication: 2017 Aug 23. - Publication Year :
- 2017
-
Abstract
- Background: Dacomitinib is a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Pre-clinical data suggest that intermittent pulsatile dosing of dacomitinib may result in inhibition of EGFR T790M.<br />Methods: We evaluated safety, pharmacokinetics and efficacy of intermittent pulsatile dacomitinib in both molecularly unselected patients and patients with lung cancers harboring EGFR T790M (Clinical Trial Registration Number NCT01858389).<br />Results: Thirty-eight patients were treated on study with pulse dacomitinib; sixteen with EGFR T790M in Cohort A and 22 who were not molecularly selected in Cohort B. One patient out of 16 patients in Cohort A had a partial response to study therapy (ORR 6.3%, 95% CI 0.2-30.2%). The median progression-free survival (PFS) in Cohort A was 2.3 months and median PFS in Cohort B was 1.6 months. The adverse event profile was similar to standard daily dose dacomitinib with the most frequent treatment-related toxicities occurring in >20% of patients being diarrhea, rash, stomatitis, nausea, dry skin, paronychia, fatigue, and decreased appetite.<br />Conclusion: Intermittent pulsatile dacomitinib is safe and relatively well tolerated but is not effective in patients that harbor EGFR T790M or in unselected patients with non-small cell lung cancer.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antineoplastic Agents pharmacokinetics
Carcinoma, Non-Small-Cell Lung mortality
Female
Humans
Lung Neoplasms mortality
Male
Middle Aged
Protein Kinase Inhibitors pharmacokinetics
Pulse Therapy, Drug
Quinazolinones pharmacokinetics
Antineoplastic Agents administration & dosage
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung pathology
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Protein Kinase Inhibitors administration & dosage
Quinazolinones administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8332
- Volume :
- 112
- Database :
- MEDLINE
- Journal :
- Lung cancer (Amsterdam, Netherlands)
- Publication Type :
- Academic Journal
- Accession number :
- 29191595
- Full Text :
- https://doi.org/10.1016/j.lungcan.2017.08.017