The Influence of Phenotype, Grapefruit Juice and Orange Juice on the Pharmacokinetics of Sunitinib in Cancer Patients

Inclusion Criteria:

* Patients with imatinib-resistant gastro-intestinal stromal cell tumor or metastatic renal cell carcinoma treated with sunitinib at a dose level of 25-50 mg sunitinib per day in a 4 weeks on/2 weeks off schedule.
* Age at least 18 years
* WHO performance status \< 2.
* At least 4 weeks since last chemotherapy, hormonal, or radiation therapy.
* A life expectancy of at least 12 weeks.
* Patients must have an adequate functional reserve as defined by: hemoglobin \> 6.0 mmol/L, White Blood Count \> 3.0 x 109/L, neutrophils \> 1.5 x 109/L, platelets \> 100 x 109/L, creatinine clearance \> 60 mL/min, bilirubin within normal limits, Alanine transaminase and aspartate transaminase \< 2.5 times the upper limit of normal (unless due to liver metastases, then \< 5 times the upper limit of normal.
* Written informed consent.

Exclusion Criteria:

* Patients with hematological malignancies
* Concurrent other chemotherapy, immunotherapy, or radiotherapy.
* Concurrent use of other substances known or likely to interfere with the pharmacokinetics of sunitinib (e.g., ketoconazole, cyclosporine A).
* Use of drugs, herbal preparations and/or dietary supplements known to influence the expression of CYP3A (e.g., phenytoin, rifampicin, St. John's wort, garlic supplements, milk thistle) within the preceding 2 weeks.
* Present clinical signs of symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan. A patient with brain and/or leptomeningeal metastases may be included only if he/she is asymptomatic on neurological examination and is not receiving corticosteroid therapy to control symptoms.
* Patients with uncontrolled infection.
* Concurrent severe medical problems unrelated to the malignancy that would limit full compliance with the study or expose the patient to extreme risk.
* Patients with pre-existing cardiac disease, including clinical congestive heart failure, cardiac arrhythmias requiring treatment, or a myocardial infarction within the preceding 3 months.
* Patients who have received another investigational drug within 30 days or 5 half-lives prior to entry in the study (whichever is longer).
* History of allergic reaction to compounds chemically related to sunitinib.
* Patients who are pregnant or breastfeeding.
* Patients of childbearing potential, not practicing adequate contraception.
* Patients that are unable to ingest oral medication and/or are known with gastric emptying disorders.