Study of Capecitabine In Patients With Solid Tumors
Status:
Completed
Trial end date:
2012-05-01
Target enrollment:
Participant gender:
Summary
Hypothesis:
Patients with TYMS 2R/2R or 2R/3R appear to be more sensitive to fluoropyrimidines,
conferring a higher risk of grade 3-4 fluoropyrimidine related toxicity and a higher response
rate compared with 3R/3R. The genotype 3R/3R is more common in East Asia and is associated
with greater tolerability to fluoropyrimidine as measured by lower toxicity but also lower
response rates. As sensitivity to fluoropyrimidine appears to be affected by TYMS genotype,
we hypothesise that patients with TYMS 3R/3R are more tolerant to standard doses of
capecitabine and require higher doses to overcome fluoropyrimidine resistance. We designed
this study to develop TYMS genotype specific dosing of capecitabine.
Aims:
1. To determine the maximal tolerated dose (MTD) of capecitabine twice a day for two weeks
followed by one week rest period (intermittent schedule) in patients with the advanced/
and or metastatic cancer based on TYMS genotype.
2. To determine a suitable phase II dose of intermittent schedule capecitabine.
3. To determine the safety and toxicity of this regimen.
4. To perform plasma pharmacokinetics of capecitabine.
5. To determine the relationship between genes of relevance in the fluoropyrimidine pathway
with pharmacokinetics and toxicity.