Article (Scientific journals)
Valproate–doxorubicin: promising therapy for progressing mesothelioma. A phase II study
Scherpereel, a; Berghmans, t; Lafitte, j.j et al.
2011In European Respiratory Journal, 37, p. 129-135
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Keywords :
valproic acid; doxorubicin; mesothelioma; histone deacetylase inhibitors; Chemotherapy
Abstract :
[en] No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy. In vitro data suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum based chemotherapy. Treatment consisted of doxorubicin (60 mg?m-2) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed. From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) o80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3– 25%), all in patients with PS 80–100. The best disease control rate was 36% (95% CI 22–51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60–70). Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80–100) patients with refractory or recurrent MM, for which no standard therapy was available.
Disciplines :
Author, co-author :
Scherpereel, a
Berghmans, t
Lafitte, j.j
Colinet, b
Richez, m
Bonduelle, y
Meert, a.p
Dhalluin, x
Leclercq, n
Paesmans, m
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Sculier, j.p
Language :
Title :
Valproate–doxorubicin: promising therapy for progressing mesothelioma. A phase II study
Publication date :
January 2011
Journal title :
European Respiratory Journal
Publisher :
European Respiratory Society, Lausanne, Switzerland
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 16 February 2011


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