Abstract
Introduction: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40% of patients being free of progression at that time point. This study followed a two-stage minimax design. Results: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8%). Median PFS was 1.5 months, 3m-PFS rate 11.1%, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.
Original language | English |
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Pages (from-to) | 195-199 |
Number of pages | 5 |
Journal | Investigational New Drugs |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2014 |
Bibliographical note
Funding Information:Acknowledgement This study was supported in part by Millennium, Merck, and the University of Wisconsin Carbone Cancer Center (P30 CA014520).
Keywords
- Bortezomib
- Non-small cell lung cancer
- Third-line
- Vorinostat
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)