Measurement of intratumoral carboplatin and 5-fluorouracil concentrations in head and neck cancer patients by in vivo microdialyses

The antitumor effect of chemotherapeutic agents can be described as a function of dose intensity, defined as the product of the concentration of the cytotoxic drug at the effect site and the time of cell exposure. Under in vitro conditions dose intensity is easily controlled. However, this is not the case in a clinical setting when solid tumors are treated, since the total dose administered is not necessarily correlated to the dose intensity in tumor cells. Data on intratumoral concentrations of anticancer drugs are scarce and only available from indirect estimations based on plasma concentrations or biopsy studies, which cannot yield sufficient data on the time profile of exposure and may overestimate intratumoral concentrations. However, information on drug concentration profiles in tumor tissue are necessary to optimize dosing and administration schedules and may help explain drug resistance in some patients. Recently, the microdialysis technique has been described for the in vivo measurement of drug concentrations in human tissues. It has also been proven feasible of measuring free, pharmacologically active intratumoral concentrations of antineoplastic agents in melanoma metastasis and breast cancer. Based on the experiences gained by those studies the present study aims at obtaining pharmacokinetic data of carboplatin and 5-fluorouracil in head and neck cancers to measure the plasma tumor transfer and to study the association between the two study drugs in one single solid tumor. Whenever possible, the patients will be followed and tumor response will be related to intratumoral pharmacokinetics of the study drugs. Whenever the volume and the condition of the tumor allows the insertion of two microdialysis probes, concentration profiles will be measured in the center and the periphery of the tumor.