ERJ Open Research (Oct 2015)

VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study

  • Thierry Berghmans,
  • Jean-Jacques Lafitte,
  • Arnaud Scherpereel,
  • Lieveke Ameye,
  • Marianne Paesmans,
  • Anne-Pascale Meert,
  • Benoit Colinet,
  • Christian Tulippe,
  • Luc Willems,
  • Nathalie Leclercq,
  • Jean-Paul Sculier,
  • for the European Lung Cancer Working Party

DOI
https://doi.org/10.1183/23120541.00029-2015
Journal volume & issue
Vol. 1, no. 2

Abstract

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Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments 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.