The purpose of this study is to investigate the effects of axitinib, a potent angiogenesis inhibitor, on tissue and clinical outcome in combination with chemotherapy given to patients with 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