Phase II Study of Valproate and Doxorubicin in Malignant Mesothelioma

Inclusion criteria

• Histological diagnosis of malignant mesothelioma
• Unresectable or inoperable malignant mesothelioma failing after at least one prior chemotherapy regimen including platinum derivatives (cisplatin or carboplatin)
• At least one evaluable or measurable CT-lesion
• Availability for participating in the detailed follow-up of the protocol
• Signed informed consent

Exclusion criteria

• Patients who are candidates for surgery with curative intent
• Patient who were previously treated with anthracyclin derivatives
• Performance status < 60 on the Karnofsky scale
• A history of prior malignant tumour, except non-melanoma skin cancer or in situ carcinoma of the cervix and cured malignant tumour (more than 5-year disease free interval)
• A history of prior HIV infection
• Polynuclear cells < 2,000/mm³
• Platelet cells < 100,000/mm³
• Abnormal coagulation tests (aPTT, PTT, prothrombin time) and/or decreased fibrinogen
• Serum bilirubin >1.5 mg/100 ml
• Transaminases more than twice the normal range
• Serum creatinine > 1.5 mg/100 ml
• Recent myocardial infarction (less than 3 months prior to date of diagnosis)
• Congestive cardiac failure (ejectional fraction of the left ventricle < 50%) or uncontrolled cardiac arrhythmia
• Uncontrolled infectious disease
• Active epilepsy needing a specific treatment
• Concomitant treatment with IMAO, carbamazepine, mefloquine, phenobarbital, primidone, phenytoïn, lamotrigine, zidovudine
• Pregnancy or refusal to use active contraception
• A known allergy to valproate acid and/or doxorubicin
• Serious medical or psychological factors which may prevent adherence to the treatment schedule