A Phase II Study Assessing the Activity of Valproate Acid Plus Doxorubicin in Refractory or Recurrent 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