Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma

To determine the effects of the addition of axitinib to standard chemotherapy on tissue samples with respect to micro-vessel density (MVD): expression of VEGF-Receptor; PDGF receptor expression; extent of necrosis and apoptosis.

To determine the safety of the addition of axitinib (to a maximum of the recommended dose of maximally 2 x 10 mg per day) to the standard treatment with cisplatin and pemetrexed.

To determine the feasibility of performing a (second) thoracoscopy after 10 weeks of the combination treatment with cisplatin, pemetrexed and axitinib.

Serum samples will be collected and tested for inhibiting effects in a tube formation and spheroid sprouting assay.

Inclusion criteria

• histologically or cytologically diagnosed malignant mesothelioma
• age > 18 years
• Medically suitable for limited surgical intervention (pleural biopsies or limited pleurectomy)
• Measurable or evaluable disease is not required
• Ability to understand the study and give signed informed consent including the approval to accept a second thoracoscopic or surgical treatment after the third course
• No previous chemotherapy
• Radiotherapy is allowed when this is given for palliation, the interval is > 4 weeks, not more than 1/3 of the bone marrow capacity or all tumor is within the irradiation field.
• WHO performance status =< 2
• Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

Hematology:

• ANC=>1.5 x 109/L,
• Platelets=>150 x 109/L,
• Hemoglobin => 6,0 mmol/l

Chemistry:

• total serum bilirubin < UNL;
• AST and ALT= < 2.5xUNL,
• AP < 5xUNL (unless bone metastases are present in the absence or any liver disease)
• Serum creatinine =< 2xUNL

Exclusion criteria

• Active uncontrolled infection, severe cardiac dysfunction or uncorrectable bleeding tendency
• Previous successful pleurodesis
• Uncontrolled hypertension
• Symptomatic peripheral neuropathy => grade 2 according to NCIC CTC,version 3.0
• Presence of symptomatic CNS metastases
• Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition
• Concomitant administration to any other experimental drugs under investigation
• Impaired renal function