Noninvasive technique predicts patients' response to chemotherapy
Positron emission tomography (PET) can non-invasively predict how much of a cancer-killing drug is absorbed by a tumor. This preliminary study, conducted in lung cancer patients, found that less than 1% of docetaxel is absorbed by the tumors.
Previously, no accurate way existed to assess how much of an anticancer drug is absorbed by a tumor or to assess what effect the drug is having on the tumor, except to resort to invasive surgery to extract samples. High costs and complexity currently prevent the large-scale use of (11C)docetaxel PET, but it is promising for investigations.
Very small tracer doses of docetaxel were radiolabeled with the positron-emitting radionuclide carbon-11. The tiny (11C)docetaxel doses were followed by PET scan in the body noninvasively. The PET scans provided information on how much drug reached the tumor, the amount absorbed by the tumor, and its effects on the tumor. The microdose protected the patients from any docetaxel-induced toxic side effects that could occur with therapeutic doses.
“A potential problem with this is the fact that the behavior of [11C]docetaxel in the tumour at tracer doses may be different from its behavior at therapeutic doses. Therefore, we investigated whether a PET study using tracer doses of [11C]docetaxel could predict tumour uptake of docetaxel at therapeutic doses,” explained study leader Astrid van der Veldt, MD, PhD, of the VU University Medical Center in Amsterdam, The Netherlands.
The researchers examined six lung cancer patients who had not been previously treated with docetaxel by two PET scans. One scan used the tracer dose of docetaxel, and the second occurred during a combined infusion of a tracer dose and a therapeutic dose (75 mg/m2) of docetaxel. When the researchers compared the tumor uptake of both the tracer and therapeutic doses of docetaxel, the tracer dose was found to correctly predict the tumor uptake of the therapeutic dose.
Additional analyses found that less than 1% of the therapeutic dose of docetaxel that was infused in the patients was finally taken up by the tumor tissue. Dr. Van der Veldt said, “This finding underscores the fact that only a small amount of drug accumulates in tumors and indicates that there is an urgent need for strategies that selectively enhance drug delivery to tumors. For that purpose, the direct effects of other, anticancer drugs on metabolism as well as drug delivery to tumors need to be investigated, as other drugs may also affect metabolism and drug delivery to tumors.”
Indeed, the uptake might also be affected by other drugs that were delivered at the same time. Dr. Van der Veldt explained, “For example, in a recent study, we have shown that the drug bevacizumab, which inhibits the creation of new blood vessels supplying the tumour, induces a rapid and significant reduction in delivery of [11C]docetaxel to tumors in non-small cell lung cancer patients.”This study was reported at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.