Safety Study of a New Schedule of Capecitabine and Docetaxel to Treat Cancers
Status:
Completed
Trial end date:
2006-03-01
Target enrollment:
Participant gender:
Summary
The combination of capecitabine and docetaxel is given to treat several different types of
cancer. Capecitabine is usually given by mouth for 14 days, and docetaxel is given IV on the
first day of capecitabine. The effects of changes in the schedule of the combination of
docetaxel and capecitabine has been examined in human breast cancer cells. A capecitabine
by-product was given orally to breast cancer-bearing animals for 14 consecutive days.
Docetaxel was given IV at a variety of times between days 1 and 15. The greatest reductions
in the volume of the cancer were seen when animals were treated with docetaxel between days 6
and 10. In two other breast cancer models, the maximal degree of delay in growth of the
tumors was achieved when the animals were treated with docetaxel on day 8 of a 14 day course
of capecitabine. The extent of tumor response was not explained by changes in tumor levels of
the enzyme thymidine phosphorylase, which is thought to be the mechanism behind the
interaction of capecitabine and docetaxel. In the breast cancer cells, capecitabine increases
the level of proteins which promote death of cancer cells, and it inhibits the levels of
proteins which block death of cancer cells.
Our hypothesis is that capecitabine and docetaxel interact with each other, because
capecitabine primes the pro-death machinery of the cell by increasing the ratio of
death-promoting proteins to death-inhibiting proteins. Cells are more susceptible to killing
by docetaxel when the pro-death machinery is activated by capecitabine.
This is a safety study to find the highest dose of capecitabine that can be given safely for
14 days, in combination with docetaxel given at a fixed dose on day 8. Once this dose of
capecitabine has been determined, an additional nine patients with tumors that can be
biopsied will be treated at this dose, and levels of capecitabine, its byproducts, and
docetaxel will be measured in the bloodstream. Biopsies of tumors will also be taken before
and after the docetaxel is given, and the levels of pro-death and anti-death proteins will be
measured.