PT  - JOURNAL ARTICLE
AU  - A. Scherpereel
AU  - T. Berghmans
AU  - J.J. Lafitte
AU  - B. Colinet
AU  - M. Richez
AU  - Y. Bonduelle
AU  - A.P. Meert
AU  - X. Dhalluin
AU  - N. Leclercq
AU  - M. Paesmans
AU  - L. Willems
TI  - Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study
AID  - 10.1183/09031936.00037310
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00373-2010
4099  - http://erj.ersjournals.com/content/early/2010/06/07/09031936.00037310.short
4100  - http://erj.ersjournals.com/content/early/2010/06/07/09031936.00037310.full
AB  - No treatment is recommended for patients with malignant mesothelioma (MM) failing after first line cisplatin-based chemotherapy (CT). In vitro data suggested that valproic acid (VA), a histone deacetylase inhibitor (HDACi), had pro-apoptotic effect and synergized with doxorubicin (D) to induce apoptosis in MM cells. Our primary endpoint was to determine response rate of combined VA and D in patients with unresectable MM failing after platinum-based CT.Treatment consisted of D (60 mg·m−2) plus VA. An interim analysis for response rate (RR) was planned after the first 16 registered patients. All the cases were centrally reviewed.From 07/2006 to 03/2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status ≥80 (76%) and an epithelioid subtype (80%). There were 7 partial responses (RR 16%; 95% CI 3–25%), all in patients with PS 80–100. Best disease control rate was 36% (95% CI 22–51%). Two toxic deaths were observed (febrile neutropenia, cerebral thrombotic event), both in patients with poor PS (60–70).VA, an HDACi, plus doxorubicin appeared an effective CT regimen in good PS (80–100) patients with refractory or recurrent MM, for which no standard therapy was available.