Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed melanoma

- Unresectable stage IV disease

- Mucosal and unknown primary disease allowed

- Measurable disease, defined as at least one lesion that can be measured in at least
one dimension as ≥ 20 mm (or as ≥ 10 mm if the CT slice thickness is ≤ 5 mm)

- Measurable lesion must be outside a previously treated area

- Must have 1 paraffin block of primary tumor and/or metastatic tissue available for
analysis of MGMT

- No ocular melanoma

- No bleeding skin metastases

- No CNS metastases (even if previously treated) by brain MRI

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- ANC ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Hemoglobin ≥ 90 g/L (transfusion allowed)

- Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in patients with liver
metastases)

- Serum creatinine < 177 μmol/L

- Proteinuria < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection

- INR ≤ 1.5

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study treatment

- No other primary tumors within the past 5 years, except adequately controlled limited
basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

- No history or evidence of CNS disease unrelated to cancer (e.g., uncontrolled
seizures) by physical/neurological examination, unless adequately treated with
standard medical therapy

- No frequent vomiting or any other pre-existing medical condition that would preclude
swallowing and/or absorption of oral medication

- No history or evidence of inherited bleeding diathesis or coagulopathy with risk of
bleeding

- No uncontrolled hypertension (i.e., systolic blood pressure > 150 mm Hg and/or
diastolic blood pressure > 100 mm Hg, measured repeatedly, despite adequate treatment
with at least two different antihypertensive drugs)

- No clinically significant (i.e., active) cardiovascular disease, including any of the
following:

- Cerebrovascular accident/stroke or myocardial infarction within the past 6
months

- Unstable angina

- New York Heart Association (NYHA) class II or greater congestive heart failure

- Serious cardiac arrhythmia (i.e., ventricular arrhythmia, high-grade
atrioventricular-block) that requires medication during the study, interferes
with regularity of the study treatment, or is uncontrolled by medication

- No serious non-healing wound, active peptic ulcer, or non-healing bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No significant traumatic injury within the past 30 days

- No uncontrolled active infection

- No known HIV infection

- No known hypersensitivity to any of the study drugs or excipients

- No evidence of any other disease, metabolic or psychological dysfunction, psychiatric
disorder, physical examination finding, or clinical laboratory finding giving
reasonable suspicion of a disease or condition that contraindicates the use of an
investigational drug, or that may affect patient compliance with study routines, or
places the patient at high risk from treatment-related complications

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior adjuvant cytokine therapy (e.g., interleukin,
interferon) or vaccine therapy and recovered

- Prior vaccine therapy for stage IV disease allowed

- Prior perfusion therapy (limb and liver) for loco-regional disease allowed

- No prior chemotherapy for metastatic disease

- No prior bevacizumab or other angiogenic inhibitors

- No prior radiotherapy to lesion(s) selected for measurement

- More than 30 days since prior treatment in a clinical trial

- More than 30 days since prior major surgery with high risk of bleeding

- More than 24 hours since prior minor surgery

- More than 10 days since prior and no concurrent full-dose oral or parenteral
anticoagulants or thrombolytic agents for therapeutic purposes

- Prophylactic use of anticoagulants is allowed (e.g., maintenance of venous
catheter)

- More than 10 days since prior and no concurrent acetylsalicylic acid (> 325 mg/day)
or clopidogrel (> 75 mg/day)

- No other concurrent non-steroidal anti-inflammatory drugs (NSAIDs)

- No concurrent dipyridamole

- No concurrent major surgery

- No concurrent radiotherapy to the target lesions

- No other concurrent experimental drugs or anticancer therapy