title: VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study.
abstract: Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing.In vitroexperiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS). Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid. 64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5-3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7-7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3-4 neutropenia and thrombopenia, respectively. Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum-etoposide.
authors.affiliation: Department of Intensive Care Unit and Thoracic Oncology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berghmans
authors.affiliation: Department of Pulmonary and Thoracic Oncology, CHRU de Lille and University of Lille II, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.affiliation: Department of Pulmonary and Thoracic Oncology, CHRU de Lille and University of Lille II, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherpereel
authors.affiliation: Data Centre, Institut Jules Bordet, Centre des Tumeurs de l'ULB, Brussels, Belgium.
authors.forename: Lieveke
authors.initials: L
authors.lastname: Ameye
authors.affiliation: Data Centre, Institut Jules Bordet, Centre des Tumeurs de l'ULB, Brussels, Belgium.
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.affiliation: Department of Intensive Care Unit and Thoracic Oncology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Meert
authors.affiliation: Department of Pneumology, Grand Hôpital de Charleroi, Gilly, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Colinet
authors.affiliation: Department of Pneumology, CH Mouscron, Mouscron, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Tulippe
authors.affiliation: Gembloux Agro-Bio Tech and Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Gembloux, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Willems
authors.affiliation: Department of Intensive Care Unit and Thoracic Oncology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leclercq
authors.affiliation: Department of Intensive Care Unit and Thoracic Oncology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Sculier