Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.

Autor: Hoang T; University of Wisconsin Carbone Cancer Center, Madison, WI, USA, txh@medicine.wisc.edu., Campbell TC, Zhang C, Kim K, Kolesar JM, Oettel KR, Blank JH, Robinson EG, Ahuja HG, Kirschling RJ, Johnson PH, Huie MS, Wims ME, Larson MM, Hernan HR, Traynor AM
Jazyk: angličtina
Zdroj: Investigational new drugs [Invest New Drugs] 2014 Feb; Vol. 32 (1), pp. 195-9. Date of Electronic Publication: 2013 Jun 01.
DOI: 10.1007/s10637-013-9980-5
Abstrakt: 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.
Databáze: MEDLINE
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