MEASUREMENT OF EXTRACELLULAR FLUID CARBOPLATIN KINETICS IN MELANOMA METASTASES WITH MICRODIALYSIS

Clinical anti-tumour efficacy of anti-cancer drugs is a function of do se intensity, i.e. the concentration-time profile in tumour tissue. He nce, information on drug concentration profiles in tumours is of criti cal importance but appropriate methods for measurement are lacking. Th e aim of the present study was to obtain, by microdialysis sampling, c oncentration-time profiles in a solid tumour (melanoma) of a model ant i-cancer drug, carboplatin, and thereby to assess the scope of microdi alysis for tumour pharmacokinetic studies in man. Six patients with cu taneous melanoma metastases at the extremities or body trunk, schedule d to receive carboplatin (400 mg m(-2) i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vi tro and in vivo with use of the retrodialysis method. Complete carbopl atin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration , time to maximum concentration, area under the curve, elimination hal f-life) were calculated for tissues and tumour/serum concentration rat ios for carboplatin were derived. Mean free concentrations of carbopla tin in cutaneous melanoma metastases reached only about 50-60% of tota l serum levels; maximal intratumoral concentrations were 7.6 (+/-2.0; s.e.m.) mu g ml(-1), mean concentrations in subcutaneous tissue were s imilar to those in tumour. The present study demonstrates that microdi alysis is a novel tool for measuring drug concentrations in solid tumo urs in humans in vivo and appears to be a valuable addition for pharma cokinetic/pharmacodynamic studies in oncology.