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

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

Tien Hoang, Toby C. Campbell, Chong Zhang, KyungMann Kim, Jill M. Kolesar, Kurt R. Oettel, Jules H. Blank, Emily G. Robinson, Harish G. Ahuja, Ron J. Kirschling, …
Investigational new drugs, Vol.32(1), pp.195-199
02/01/2014
DOI: 10.1007/s10637-013-9980-5
PMCID: PMC4310688
PMID: 23728919
url
https://www.ncbi.nlm.nih.gov/pmc/articles/4310688View
Open Access

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.
Life Sciences & Biomedicine Oncology Pharmacology & Pharmacy Science & Technology

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