Carboplatin and Paclitaxel in combination with either vorinostat or placebo for
first-line therapy of advanced non-small-cell lung cancer.
Author(s): Ramalingam SS, Maitland ML, Frankel P, Argiris AE, Koczywas M, Gitlitz B, Thomas
S, Espinoza-Delgado I, Vokes EE, Gandara DR, Belani CP.
Affiliation(s): Emory University, Winship Cancer Institute, 1365 Clifton Rd, C-3090, Atlanta, GA
30322, USA. suresh.ramalingam@emory.edu
Publication date & source: 2010, J Clin Oncol. , 28(1):56-62
PURPOSE Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by
both histone and nonhistone-mediated mechanisms. It also enhances the anticancer
effects of platinum compounds and taxanes in non-small-cell lung cancer (NSCLC)
cell lines. This phase II randomized, double-blinded, placebo-controlled study
evaluated the efficacy of vorinostat in combination with carboplatin and
paclitaxel in patients with advanced-stage NSCLC. PATIENTS AND METHODS Patients
with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned
(2:1) to carboplatin (area under the curve, 6 mg/mL x min) and paclitaxel (200
mg/m(2) day 3) with either vorinostat (400 mg by mouth daily) or placebo.
Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a
maximum of six cycles. The primary end point was comparison of the response rate.
Results Ninety-four patients initiated protocol therapy. Baseline patient
characteristics were similar between the two arms. The median number of cycles
was four for both treatment arms. The confirmed response rate was 34% with
vorinostat versus 12.5% with placebo (P = .02). There was a trend toward
improvement in median progression-free survival (6.0 months v 4.1 months; P =
.48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat
arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P <
.05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more
frequent with vorinostat. CONCLUSION Vorinostat enhances the efficacy of
carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a
promising therapeutic strategy for treatment of NSCLC.
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