LONG-TERM PHARMACOKINETIC BEHAVIOR OF PLATINUM AFTER CISPLATIN ADMINISTRATION

Purpose: The platinum concentration in plasma was studied in 19 patients treated by 3 or 4 successive courses of chemotherapy including cisplatin for head and neck cancers. Methods: Cisplatin was given i.v. daily at 25 mg/m(2) by 1-h infusions for 4 days every 3 weeks. Total and ultrafiltrable platinum were measured in plasma using an inductively coupled plasma mass spectrometry (ICPMS) technique. Results: A progressive accumulation of total platinum in plasma was observed with consecutive infusions. The mean (+/- SD) total plasma platinum level detected at the end of cisplatin infusion was 1134 +/- 234 1407 +/- 268, and 1618 +/- 282 mu g/l at the end of the first, second, and third courses, respectively. The minimal platinum concentration measured before the second and third courses also increased to 221 +/- 59 and 309 +/- 76 mu g/1, respectively. The steady state was not reached before the third course. However: differences in the evolution of platinum plasma levels were found among the 19 patients. In 14 patients the pharmacokinetics of platinum was characterized by low initial levels, a progressive accumulation, and a long terminal half-life with a very late steady state. In 5 patients, the pharmacokinetic behavior of platinum was different: platinum levels were directly high, without progressive accumulation, the steady state being reached as early as the first course. Significant levels of ultrafiltrable platinum were found throughout the treatment, even during the intervals between courses with this very sensitive analytical method. A close equilibrium between ultrafiltrable and total platinum (ratio, 6%) persisted for as long as 3 weeks after cisplatin administration. Discussion: These results underline the importance of individual differences in platinum metabolism. The relationship between total and ultrafiltrable platinum are discussed.