Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study

Area of Science:

• Oncology
• Pharmacology

Background:

• Malignant mesothelioma (MM) lacks effective treatments after first-line chemotherapy.
• In vitro studies suggested valproic acid (a histone deacetylase inhibitor) and doxorubicin synergize to induce apoptosis in MM cells.

Purpose of the Study:

• To determine the response rate of combined valproic acid and doxorubicin in unresectable MM patients post-platinum-based chemotherapy.
• To evaluate the safety and efficacy of this novel combination regimen.

Main Methods:

• 45 eligible patients with pleural MM were enrolled.
• Treatment involved doxorubicin (60 mg·m⁻²) plus valproic acid.
• Response rate was the primary endpoint, with interim analysis after 16 patients.

Main Results:

• Seven partial responses were observed (response rate 16%; 95% CI 3-25%), all in patients with good performance status (PS 80-100).
• The best disease control rate was 36% (95% CI 22-51%).
• Two toxic deaths occurred in patients with poor PS (60-70).

Conclusions:

• Valproic acid plus doxorubicin demonstrated efficacy in patients with good performance status and refractory or recurrent MM.
• This combination represents a potential new therapeutic option for MM patients lacking standard treatment alternatives.